Our study showed that KSQ‐4279 strikingly intensified the cytotoxicity of multiple classical chemotherapeutic drugs in ABCB1/ABCG2/ABCC1‐induced MDR cancers independent of its own cytotoxicity in vitro, and remarkably improved chemotherapeutic efficacy not only in ABCB1/ABCG2/ABCC1‐overexpressing tumor xenografts in vivo, but also in ABCB1‐overexpressing clinical lung cancers ex vivo. The gene discussed is ABCC1; the disease is lung cancer.