Overall, KSQ‐4279 effectively conquered the ABCB1‐, ABCG2‐, or ABCC1‐induced MDR in vivo, and significantly relieved the ABCB1‐mediated MDR in clinical lung cancer patients’ ex vivo specimen models, which encouraged further study in combination of KSQ‐4279 and chemotherapy in the patients with MDR cancer in clinic. Here, ABCB1 is linked to lung carcinoma.