Abstract: Lung cancer is one of the malignant tumors with the highest mortality in the world. Epidermal growth factor receptor tyrosine kinase inhibitors（EGFR-TKIs）significantly improve the quality of life of advanced non-small cell lung cancer（NSCLC），and prolong the overall survival. However，only a certain subpopulation of lung cancer patients carrying specific activating mutations in EGFR respond clinically to EGFR-TKIs.Even among these patients，the median progression-free survival（PFS）is about 12 months owing to drug resistance. Recently，quite a few patients acquired drug resistance with NSCLC transitioned to small cell lung cancer（SCLC）were reported. In this review，we discuss the recent advances in the understanding of the phenomenon and possible mechanisms for the conversion of NSCLC into SCLC. The treatment strategies of patients with EGFR mutations in SCLC will be recommended according to the therapy scheme after EGFR-TKIs resistance of NSCLC and treatment proposal of the individual reported.