In this work, we first disclosed the widely potent reversing effects of KSQ‐4279, a highly‐selective USP1 inhibitor currently in clinical trial (Phase I) for advanced solid tumors (NCT05240898), on ABCB1/ABCG2/ABCC1‐induced MDR cancers, and the exact mechanisms behind were elucidated. This evidence concerns the gene USP1 and cancer.