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CORRESP

 June 21, 2012

 VIA EDGAR

 Jeffrey Riedler, Assistant Director

Jennifer Riegel, Special Counsel

 Nandini
Acharya, Staff Attorney

 Division of Corporation Finance

 Securities and Exchange Commission

 100 F Street, N.E.

Washington, D.C. 20549

Re:

RXi Pharmaceuticals Corporation

Registration Statement on Form S-1

Filed May 18, 2012

File No. 333-181534

 Ladies and Gentlemen:

 On behalf of RXi Pharmaceuticals Corporation (the “Company”), we are submitting to the Securities and Exchange Commission (the “Commission”) the Company’s response to the comment
from the staff of the Division of Corporation Finance (the “Staff”) contained in the comment letter from the Commission dated June 11, 2012 regarding the Company’s Registration Statement on Form S-1 (File No. 333-181534),
which was filed with the Commission on May 18, 2012 (the “Registration Statement”).

 The comment has been
reproduced below in italics, followed by the Company’s response. Capitalized terms used but not defined in this letter are intended to have the meanings ascribed to such terms in the Registration Statement.

1. Please provide us with your basis for determining that the transaction is appropriately characterized as a transaction that is
eligible to be made under Rule 415(a)(1)(i) rather than a primary offering. In your analysis, please address the following among any other relevant factors:

•

 The number of selling stockholders and the percentage of the overall offering made by each stockholder;

•

 The amount of shares involved;

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•

 The date on which and the manner in which each selling stockholder received the shares and/or the overlying securities;

•

 The relationship of each selling stockholder with the company, including an analysis of whether the selling stockholder is an affiliate of the
company;

•

 Any relationships among the selling stockholders;

•

 The discount at which the selling stockholders will purchase the common stock underlying the preferred stock upon conversion;

•

 Whether or not any of the selling stockholders is in the business of buying and selling securities; and

•

 Whether under all the circumstances it appears that the selling stockholders are acting as a conduit for the company.

 Alternatively, please name the selling stockholders as underwriters and register the offering on a registration
statement for which you are eligible to conduct a primary offering consistent with Rule 415. Please see our Compliance and Disclosure Interpretation 612.09 available at http://www.sec.gov/divisions/corpfin/guidance/securitiesactrules-interps.htm for
further guidance.

 Response to Comment 1:

 For the reasons set forth below, the Company respectfully submits that the offering to be registered pursuant to the Registration Statement is a valid secondary offering and may be registered as
contemplated by the Registration Statement, and that the selling stockholders are not “underwriters” within the meaning of Section 2(a)(11) of the Securities Act of 1933, as amended (the “Act”).

Background

 On September 24, 2011,
the Company entered into a Securities Purchase Agreement (the “Purchase Agreement”) with the two selling stockholders identified in the Registration Statement (the “Investors”), both of whom are accredited investors, for the sale
of 9,500 shares of Series A Convertible Preferred Stock (the “Preferred Stock”) for aggregate consideration of $9.5 million. This financing transaction pursuant to which the Preferred Stock was offered and sold is referred to herein as the
“Financing.” The Financing closed on April 27, 2012 (the “Closing Date”) following the registration under the Act of the distribution of shares of the Company’s common stock pursuant to a spin-out that was effected
through a dividend declared and paid by Galena Biopharma, Inc (“Galena”).

 The Preferred Stock was issued on the Closing Date
pursuant to the exemption from registration provided by Section 4(2) of the Act. In the Purchase Agreement, the Investors made customary representations and warranties regarding their investment intent, including representations that they were
purchasing their securities for their own accounts, for investment purposes and not for the purpose of effecting any distribution of the securities in violation of the Act.

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 Preferred Stock Conversion Features

 Pursuant to the terms of the Certificate of Designations for the Preferred Stock (the “Certificate of Designations”), the Preferred Stock is convertible into common stock, par value $0.0001 per
share (the “Common Stock”), at a fixed conversion rate. The number of shares of Common Stock issuable upon conversion of the Preferred Stock is only subject to adjustment in the event of a stock split, reverse stock split or similar
recapitalization event. In no event is the conversion price for the Preferred Stock subject to adjustment based on future issuances of capital stock by the Company (i.e., there are no anti-dilution features). Additionally, the Preferred Stock is not
entitled to vote in the election of directors and generally has no voting rights, other than with respect to certain extraordinary events, such as an amendment to the rights, preferences or privileges of the Preferred Stock or any liquidation or
dissolution of the Company.

 The Preferred Stock is subject to a “blocker” provision contained in the Certificate of Designations,
which prevents the conversion of the Preferred Stock to the extent that the holder would, after conversion, beneficially own more than 9.999% of the Company’s issued and outstanding Common Stock. Accordingly, the selling stockholders will not,
by virtue of their ownership of the Preferred Stock and the Common Stock underlying the Preferred Stock (the “Conversion Shares”), beneficially own more than 9.999% of the Company’s voting securities. Of the total number of Conversion
Shares underlying the Preferred Stock, approximately 20% of the Conversion Shares are being registered for resale under the Registration Statement.

 Not a “Toxic” Financing

 The terms of the Financing do not include any conversion
price “re-sets”, floating price conversion rights or other “toxic” features that have historically prompted the Staff’s concerns regarding financing transactions that have sometimes been characterized as “extreme
convertible” transactions. The Certificate of Designations does not contain any conversion price adjustment mechanisms, including anti-dilution adjustments, other than customary adjustments that would apply in the case of a stock split, reverse
stock split and similar recapitalization event. Based on prior guidance provided by senior members of the Staff, the Company believes that the absence of any adjustment mechanisms would not raise concerns among the Staff with respect to the
Staff’s interpretation of Rule 415.

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 Rule 415 Analysis

 In 1983, the Commission adopted Rule 415 under the Act to permit the registration of offerings to be made on a delayed or continuous basis. Rule 415 specifies certain conditions that must be met by an
issuer in order to avail itself of the Rule. In relevant part, Rule 415 provides:

 “(a) Securities may be
registered for an offering to be made on a continuous or delayed basis in the future, Provided, That:

 (1) The
registration statement pertains only to:

 (i) Securities which are to be offered or sold solely by or on behalf
of a person or persons other than the registrant, a subsidiary of the registrant or a person of which the registrant is a subsidiary;....[or]

 (x) Securities registered (or qualified to be registered) on Form S-3 or Form F-3 (§239.13 or §239.33 of this chapter) which are to be offered and sold on an immediate, continuous or delayed
basis by or on behalf of the registrant, a majority-owned subsidiary of the registrant or a person of which the registrant is a majority-owned subsidiary....”

 Under Rule 415(a)(1)(i), an issuer may register shares to be sold on a delayed or continuous basis by selling stockholders in a bona fide secondary offering without restriction.

In the event that an offering registered in reliance on Rule 415(a)(1)(i) is deemed to be an offering that is “by or on behalf of the
registrant” as specified in Rule 415(a)(1)(x), Rule 415 contains additional limitations. Rule 415(a)(4) provides that:

“In the case of a registration statement pertaining to an at the market offering of equity securities by or on behalf of the
registrant, the offering must come within paragraph (a)(1)(x) of this section. As used in this paragraph, the term ‘at the market offering’ means an offering of equity securities into an existing trading market for outstanding shares of
the same class at other than a fixed price.”

 As a result, if an offering that purports to be a secondary offering is characterized as an
offering “by or on behalf of the registrant,” Rule 415 is only available to register an “at the market offering” if the registrant is eligible to use Form S-3 or Form F-3 to register a primary offering.

In the event that the offering registered by the Registration Statement is recharacterized as a primary offering on behalf of the Company: (i) the
offering would have to be made on a fixed price basis (in other words, the Investors would not be able to sell their securities at prevailing market prices) unless the Company is eligible to use Form S-3 for a primary offering, (ii) the
Investors would be deemed to be “underwriters” with respect to the Financing (with the attendant liabilities under Section 11 of the Act), and (iii) in accordance with the Staff’s interpretive position, Rule 144 would not be
available to the Investors to effect resales of their securities.

 Because of the requirements of Rule 415, the Staff’s interpretation of
Rule 415 has a significant impact on the ability of a selling stockholder to sell the Common Stock registered on the Registration Statement. Because recharacterizing the offering as “by or on behalf of the registrant” has such a
significant impact, and a mischaracterization can have a chilling effect on the ability of

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smaller public companies, such as the Company, to raise capital, the Company respectfully submits that the Staff should only recharacterize a secondary offering as being on behalf of a registrant
after a review of the relevant facts and circumstances, including the factors set forth in Interpretation 214.02 (the “Interpretation”) from the Staff’s Compliance and Disclosure Interpretations, which states that:

“It is important to identify whether a purported secondary offering is really a primary offering, i.e., the selling stockholders are
actually underwriters selling on behalf of an issuer. Underwriter status may involve additional disclosure, including an acknowledgment of the seller’s prospectus delivery requirements. In an offering involving Rule 415 or Form S-3, if the
offering is deemed to be on behalf of the issuer, the Rule and Form in some cases will be unavailable (e.g., because of the Form S-3 ‘public float’ test for a primary offering, or because Rule 415 (a)(l)(i) is available for secondary
offerings, but primary offerings must meet the requirements of one of the other subsections of Rule 415). The question of whether an offering styled a secondary one is really on behalf of the issuer is a difficult factual one, not merely a
question of who receives the proceeds. Consideration should be given to how long the selling stockholders have held the shares, the circumstances under which they received them, their relationship to the issuer, the amount of shares involved,
whether the sellers are in the business of underwriting securities, and finally, whether under all the circumstances it appears that the seller is acting as a conduit for the issuer.” (emphasis added)

As the Interpretation indicates, the question is a “difficult” and “factual” one that involves an analysis of many factors and
“all the circumstances.”

 Each of the relevant factors listed in the Interpretation is discussed below in the context of the
Financing. Based on a proper consideration of all of those factors, the Company believes that the Staff should conclude that the Registration Statement does relate to a valid secondary offering and that potentially all of the Conversion Shares can
be registered for sale on behalf of the Investors pursuant to Rule 415.

 How Long the Selling Stockholders Have Held the Shares

 Presumably, the longer shares are held, the less likely it is that the selling stockholders are acting as a mere conduit for the Company.
Here, the Investors have now held the shares (including the holding period for Preferred Stock, for which “tacking” would be permitted under Rule 144) for approximately two months as of the date of this letter (we further note that the
Investors became contractually obligated to purchase the Preferred Stock in September 2011, which is nearly nine months ago). Even this shorter two-month holding period is substantially longer than the period required by the Staff for valid
“PIPE” transactions.

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 The Staff’s “PIPEs” interpretation is codified as Interpretation 139.11 (the “PIPEs
Interpretation”). The PIPEs Interpretation provides in relevant part that:

 “In a PIPE transaction, a company will be
permitted to register the resale of securities prior to their issuance if the company has completed a Section 4(2)-exempt sale of the securities (or in the case of convertible securities, of the convertible security itself) to the
investor, and the investor is at market risk at the time of filing of the resale registration statement.... The closing of the private placement of the unissued securities must occur within a short time after the effectiveness of the resale
registration statement.” (emphasis added)

 The PIPEs Interpretation contemplates that a valid secondary offering could be registered
under the Act prior to closing and that the resulting resale transactions could occur immediately following the closing of the initial private placement. Because no specific holding period is required for a PIPE transaction to be a valid
secondary offering, it stands to reason that a holding period of approximately two months must also be sufficient for a valid secondary offering.

 This conclusion comports with long-standing custom and practice in PIPE transactions, where investors require that a registration statement be filed shortly after closing (typically within 30 days) and
declared effective shortly thereafter (typically within 90 days from closing). Similar customary time periods apply in the case of the Financing.

 The Circumstances Under Which The Investors Received the Shares

 As described above, the
securities covered by the Registration Statement underlie the Preferred Stock, which was issued in a valid private placement that complied in all respects with the PIPEs Interpretation and Section 4(2) of the Act. As noted above, the
Certificate of Designations contains no “toxic” provisions or other terms that would be expected to merit any special concerns by the Staff. The Investors purchased their securities for investment and specifically represented that they
were not acquiring their securities with the purpose or intent of effecting a distribution in violation of the Act. There is no evidence to suggest that those representations are false and the Company respectfully submits that there is no basis for
concluding that the Investors do not have the intention or ability to hold their shares for investment purposes for an indefinite period. Based on reports of recent statements of policy of the Staff relating to Rule 415, the Company believes tha