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Mail Stop 6010          January 25, 2008   Tod Woolf, Ph.D.  Chief Executive Officer  RXi Pharmaceuticals Corporation  One Innovation Drive  Worcester, Massachusetts 01605
 Re: RXi Pharmaceuticals Corporation
  Registration Statement on Form S-1/A
  Filed January 10, 2008
  File No. 333-147009

Dear Dr. Woolf:
  We have reviewed your filing and have the following comments.  Where indicated, we think you should re vise your document in response to these comments.  If
you disagree, we will consider your explanation as to why our comment is inapplicable or
a revision is unnecessary.  Please be as deta iled as necessary in your explanation.  In
some of our comments, we may ask you to provi de us with information so we may better
understand your disclosure.  After reviewing th is information, we may raise additional
comments.   Please understand that the purpose of our re view process is to assist you in your
compliance with the applicable disclosure  requirements and to  enhance the overall
disclosure in your filing.  We look forward to  working with you in these respects.  We
welcome any questions you may have about our comments or any other aspect of our review.  Feel free to call us at the telephone numbers listed at the end of this letter.
 General

 1. Unless otherwise stated, all comments are applicable to the distribution prospectus, award prospectus and resale prospectus.
 2. We are reissuing part of prior comment 6.  Throughout the registration statement,
you should clearly articulate the basis of the various beliefs and assertions you
make.  In each of the below statements and each similar case throughout the filing, you should disclose the basis for your belief.  If any of your assertions or

Tod Woolf, Ph.D.
RXi Pharmaceuticals Corporation  January 25, 2008 Page 2
beliefs are not supported by ample evidence or knowledge, you should delete them.  Alternatively, in each case and as applicable, clarify that these are goals or beliefs articulating what you hope to achieve.

a. Page 2: “There are many well-studied genes associated with numerous
diseases that have been identified bu t have been difficult to target with
normal medicinal chemistry and which we believe RNAi technology may be able to target and, therefore,  potentially treat such diseases.”

b. Page 35: “We believe we will be able to discover and develop lead compounds and move them into and through development for potential commercialization more efficiently than traditional drug development approaches.”

c. Page 52: “We believe that the RNAi platform will create a successful new class of potent and specific therapeuti cs with significant advantages over
traditional drug development methods. These advantages include: high specificity for targeted genes; hi gh potency (low doses); potential
interference with the ex pression of any gene; and accelerated development
of lead compounds.”  In addition, we note you also make similar statements, without support, on page  53, to the extent you cannot support
these statements, please delete them.

d. Page 53: “rxRNA is an alternativ e to classic siRNA used by other
companies developing RNAi therapeu tics and is: up to 100x more active
than conventional siRNA (depending on th e target site), nu clease resistant,
readily manufactured, comprised of el ements from RXi’s IP portfolio, and
potentially more specific for the target gene.”

e. Page 54: “We believe that nanotrans porter delivery has the following
potential advantages: inhibition of li ver target with 1 mg RNAi compound
per kg of body weight; no immune stimulation detected; defined particle size; and readily formulated.”
 f. Page 55: “We believe RNAi compounds have the potential to target any gene.”

g. Page 56: “RNAi reagents targeting mu ltiple genes could be developed to
treat cancers originated from malfunctioning of multiple intracellular pathways.”

h. Page 56: “RNAi may be used to inhibit cell division in non-cancerous
tissues which are damaged by chemothera py in order to pr otect these cells
from chemotherapy. RNAi screening methods may potentially also be

Tod Woolf, Ph.D.
RXi Pharmaceuticals Corporation  January 25, 2008 Page 3
used to rapidly prioritize molecular targets within large gene families by conducting in vitro experiments to id entify which gene family members
are the most appropriate targets to pursue.”
 Prospectus Summary, page 1

3. We note our prior comment 12 and reissue it in part.  In the Prospectus Summary,
please clarify how much of their profe ssional time your advisory board members
will devote to the company, as opposed to other professional endeavors, and
explain, if true, that they are not employees of the company, have other
professional commitments that require significantly more of their professional time and attention than any obligations th ey have to the company, and that they
have no obligations or duties to perform a ny advisory services for the company or
remain as advisors to the company.  Provide similar disclosure in the Business section.
 Risk Factors, page 10

 “We will be subject to competition and may not be able to compete successfully.”  Page
13

4. Please expand your discussion to discuss the additional risk that occurs when a competitor’s drug, which has been granted orphan drug status, is approved by the FDA.
 “We use biological and hazardous materials…” page 21

5. We are reissuing prior comment 29.  Please disclose your level of workers’
compensation insurance coverage and brie fly describe what potential liabilities
are and are not covered.
 Executive Compensation, page 74

 2007 Executive Compensation Components, page 75

 Performance-Based Compensation, page 76

6. Please disclose any performance goals set by the compensation committee or board for 2007, including, but not limited to, the performance goals in connection with Mr. DiPalma’s and Dr. Samarsky’s awards.

7. Please also revise to state any target  performance based compensation amounts
for the other executive officers which were set in 2007.

Tod Woolf, Ph.D.
RXi Pharmaceuticals Corporation  January 25, 2008 Page 4
Summary Compensation Table, page 78

8. Please revise the table to provide a foot note which discloses all assumptions made
in the valuation of the option awards.  S ee Instruction 1 to It em 402(c)(v) and (vi)
of Regulation S-K.

9. Please revise footnote 1 to provide disclo sure regarding any formula or criteria
that will be used and any other pertin ent information in determining the bonus
amount.  See Telephone Interpretation J.8B.
 Director Compensation, page 87

10. Please revise the table to provide a foot note which discloses the aggregate number
of option awards outstanding at fiscal y ear end.  See the Instruction to Item
402(k)(2)(iii) and (iv) of Regulation S-K.

Certain Relationships and Re lated Transactions, page 92
 Relationships with Employees, page 92

11. Please file a copy of your license  agreement with Invitrogen.
 Material United States Federal In come Tax Considerations, page 100

12. Please revise to clearly state that the disc losure in this section is the opinion of
Troy & Gould, rather than stating that  it has delivered an opinion “to the
following effects.”

Legal Matters, page 103

13. Please disclose in the distribution prosp ectus the required information regarding
the interests of Mr. Hillsberg and Troy & Gould pursuant to Item 509 of Regulation S-K, as we not e that Troy & Gould is  providing a tax opinion
regarding this transaction.

RXI Pharmaceuticals Corporation and Predecessor Carve-Out Financial
Statements

RXI Pharmaceuticals Corporation and Predecessor Carve-Out Statements of Expenses
and Statements of Cash Flows, pages F-4 and F-6, respectively.

14. With regards to the cumulative data presented for the period from April 3, 2006
(date of incorporation) to September 30, 2007, please in clude all financial data
related to the period from January  1, 2003 through September 30, 2007 which

Tod Woolf, Ph.D.
RXi Pharmaceuticals Corporation  January 25, 2008 Page 5
would include predecessor financial inform ation. In that regard, please remove the
parenthetical reference to Successor unde r that column. Please revise this
presentation throughout the filing.

Notes to Financial Statements

5. Development Stage Supplemental Equity Disclosure, page F-15

15. We acknowledge your response to our commen t 60.  Please revise your disclosure
added on pages 28, 35 and 46 to clarify that you include the 462,112 shares of
common stock in determining your $5.00 share value because you committed to
issue these shares prior to the date of your third-party valuation consistent with
your response.

16. In addition, with regards to your  common stock issuance of 188,387 on
September 28, 2007, please revise throughout the filing, specifically pages 28 and
35, the actual price of $5.19 per share as indicated in this footnote.

17. We acknowledge your response to our commen t 61.  Please revise your disclosure
added in footnote (B) to your table to clar ify that the pro rata share of offering
costs allocated to RXi rela tes to the private offering conducted by CytRx to fund
your capital contribution consis tent with your response.

18. In addition, as previously requested in our comment 61, please revise your
liquidity discussion in MD&A to provide an  indication of the co sts you expect to
incur in this offering as indicated on pa ge B-22. We did not note any revision to
your disclosure with regards to this comment.
 9. Commitments and Con tingencies, page F-16

19. Refer to your response to our comment 62 and we reissue our comment.  It appears from footnote 3 that the paym ents included in the table represent
minimum annual royalty payment obligat ions. Please revise your footnote
disclosure to quantify the milestone pa yment amounts that maybe required under
your agreements which you state that you have omitted from the table.  In
addition, please discuss, similar to the discussion provided in  your response, how
these potential milestone payments were determined.
 Resale Prospectus

 20. We note your response to prior comment 66.  It appears that CytRx’s proposed
offering of shares in what you have termed the “Resale Prospectus” would be a primary offering and that CytRx would be  an underwriter.  Since RXi is not
eligible to conduct a primary offering on Form S-3 or “at-the-market” under Rule

Tod Woolf, Ph.D.
RXi Pharmaceuticals Corporation  January 25, 2008 Page 6
415(a)(4),  you should remove CytRx as a selling sharehol der in this offering.  If
you would like to register the offer and sa le of these shares of RXi common stock,
you should register that transaction at a fixed price and name CytRx as an
underwriter.

21. As to UMMS’s resale of its RXi shares, in the “Resale Prospectus” please provide
the pricing information required by Item 501(b)(3) of Regulation S-K.  Absent a
market price, disclosing that the shares would be sold at market does not satisfy
this Item requirement.  Please revise the cover page of the “R esale Prospectus” to
state, “The selling shareholder will sell at a price of $x.xx (or a range) per share
until our shares are quoted on the NASDAQ Capital Market and thereafter at prevailing market prices or privately negotiated prices.”
 Selling Stockholders, page B-85

 22. It appears that UMMS is  offering 462,112 shares under th is “Resale Prospectus;”
please revise your table accordingly.

Part II

Item 17.  Undertakings

23. Please review Item 512 of Regulation S-K and provide all undertakings required
by that Item.  For example, we note that the offering described in the “Resale
Prospectus” is an offering under Ru le 415 and you have not provided the
undertaking required by Item 512(a).

* * *
  As appropriate, please amend your regist ration statement in response to these
comments.  You may wish to provide us with marked copies of the amendment to expedite our review.  Please furnish a cove r letter with your amendment that keys your
responses to our comments and provides any requested information.  Detailed cover
letters greatly facilitate our review.  Please understand that we may have additional comments after reviewing your amendmen t and responses to our comments.
  We direct your attention to Rules 46 0 and 461 regarding requesting acceleration
of a registration statement.  Please allow ad equate time after the filing of any amendment
for further review before submitting a request for acceleration.  Please provide this request at least two business days in a dvance of the requested effective date.

Tod Woolf, Ph.D.
RXi Pharmaceuticals Corporation  January 25, 2008 Page 7
You may contact Sasha Parikh at (202)  551-3627 or Mark Brunhofer at (202)
551-3638 if you have questions regarding comm ents on the financial statements and
related matters.  Please c ontact Jennifer Riegel at (202) 551-3575, Michael Reedich,
Special Counsel, at (202) 551-3612 or me at (202) 551-3715 with any other questions.           S i n c e r e l y ,             J e f f r e y  R i e d l e r          A s s i s t a n t  D i r e c t o r   cc: Marc Rubenstein, Esq.
Ropes & Gray LLP One International Place Boston, MA 02110-2624