In this study, CDK4/6is prevent the growth and chemoresistance formation of Small cell lung cancer (SCLC) via AMBRA1‐CDK6‐TFEB/TFE3 signal pathway.  CDK6 is the major upregulated factor during the resistance period of SCLC chemotherapy, and CDK4/6 inhibitors induce impaired autophagy and cell apoptosis by regulating lysosome function. The gene discussed is TFEB; the disease is small cell lung carcinoma.