The invention relates to small molecule drugs targeting an MDM2 zinc finger domain and antineoplastic application thereof. RPL11 is combined with a C4 zinc finger region of an MDM2 central domain to play the most important role in p53 activation and ribosome stress sensing. A key site targeting the MDM2 zinc finger domain is found by an applicant, and is used for screening out a small molecule compound S9, it is shown by in vitro and vivo experiments that S9 has obvious effects in inhibiting tumor cell proliferation and good clinical application prospects.