In the current study, we found that bufalin, a well‐established small molecule inhibitor of SRC‐1, combined with PD‐L1 antibody treatment in mice significantly reduced PD‐L1 expression and enhanced antitumor efficacy in CRC models, suggesting that bufalin improves the antitumor efficacy of PD‐L1 antibody treatment by down‐regulating PD‐L1 level, at least in part, by SRC‐1 in tumor cells. This evidence concerns the gene NCOA1 and neoplasm.