United States securities and exchange commission logo

                              September 23, 2021

       Ren   Russo, Pharm.D.
       President and Chief Executive Officer
       Xilio Therapeutics, Inc.
       828 Winter Street
       Waltham, Massachusetts 02451

                                                        Re: Xilio Therapeutics,
                                                            Amendment No. 1 to
Draft Registration Statement on Form S-1
                                                            Submitted September
14, 2021
                                                            CIK No. 0001840233

       Dear Dr. Russo:

             We have reviewed your amended draft registration statement and
have the following
       comments. In some of our comments, we may ask you to provide us with
information so we
       may better understand your disclosure.

              Please respond to this letter by providing the requested
information and either submitting
       an amended draft registration statement or publicly filing your
registration statement on
       EDGAR. If you do not believe our comments apply to your facts and
circumstances or do not
       believe an amendment is appropriate, please tell us why in your

             After reviewing the information you provide in response to these
comments and your
       amended draft registration statement or filed registration statement, we
may have additional

       Amendment No. 1 to Draft Registration Statement on Form S-1

       Prospectus Summary
       Our Pipeline, page 4

   1.                                                   Please revise your
pipeline table to remove your targeted cytokine program. Given the
                                                        early stage of
development of this program, it does not appear to be sufficiently material
                                                        to your business to
warrant inclusion in your pipeline table.
       Our History and Team, page 8

   2.                                                   We note your response
to prior comment 4. The identification of past life science
                                                        investors appears to
suggest that potential investors may consider investments made by
                                                        these investors as a
factor in making their investment decisions without knowing the
 Ren   Russo, Pharm.D.
Xilio Therapeutics, Inc.
September 23, 2021
Page 2
       amount of their investment in total or on a per share basis, their
investment strategies or
       whether these investors continue to hold their shares. Additionally, as
these shareholders
       are not subject to the reporting requirements of Section 16, investors
will not know when
       they decide to sell their shares. Therefore, we continue to believe the
disclosure is
       inappropriate for the registration statement and ask that it be removed.
Our Strategy, page 8

3.     We note your disclosure that your strategy is to enable a rapid
transition to randomized
       registration-enabling trials in a range of solid tumor indications for
XTX101. Please revise
       this statement and any similar disclosure to remove any implication that
you will be
       successful in advancing your product candidates in a rapid or
accelerated manner as such
       statements are speculative.
       You may contact Michael Fay at 202-551-3812 or Vanessa Robertson at
202-551-3649 if
you have questions regarding comments on the financial statements and related
matters. Please
contact Ada D. Sarmento at 202-551-3798 or Tim Buchmiller at 202-551-3635 with
any other

FirstName LastNameRen   Russo, Pharm.D.
                                                             Division of
Corporation Finance
Comapany NameXilio Therapeutics, Inc.
                                                             Office of Life
September 23, 2021 Page 2
cc:       Cynthia T. Mazareas, Esq.
FirstName LastName