Although the specific mechanism of macropinocytosis induction in this process needed to be further elucidated, we propose a novel concept whereby co‐treatment of MDR cancer cells with routine anti‐MDR therapy together with the NPC1L1 inhibitor ezetimibe significantly reduces the residual persister cell pool by inducing oxidative stress‐dependent lethal macropinocytosis. This evidence concerns the gene NPC1L1 and cancer.