The Fc fragment of IgG binding protein (FCGBP) exhibits differential expression across various tumor types. but its role in cancer progression remains underexplored. This research discovered that FCGBP is downregulated in colorectal cancer (CRC) cells and is negatively associated with poor prognosis. Overexpression of FCGBP inhibited the growth of P53 wild-type CRC cells both in vitro and in vivo. Mechanistically, immunoprecipitation experiments revealed that FCGBP competitively binds to MDM2, thereby attenuating the formation of the P53/MDM2 complex. This, in turn, reduces P53 ubiquitination and stabilizes the protein. Our findings reveal a novel mechanism through which FCGBP significantly inhibits CRC cell growth and propose a new targeted therapeutic strategy for CRC treatment.