This is the first study to investigate the combination of USP1 inhibitor (KSQ‐4279) with traditional chemotherapeutic drugs in reversing MDR, which surprisingly hinted ABCB1, ABCG2, and ABCC1 as the new targets of KSQ‐4279, and advocated this promising combination therapy in clinical refractory MDR cancers. This evidence concerns the gene USP1 and cancer.