In this study, our Food and Drug Administration (FDA)‐approved drug screening reveals that abemaciclib, a cyclin‐dependent kinase 4/6 (CDK4/6) inhibitor, dramatically promotes the proteasome‐dependent degradation of YAP1, thereby inhibiting tumor progression in CRC cells and patient‐derived xenograft models. This evidence concerns the gene CDK4 and colorectal carcinoma.