Lung cancer is the worldwide leading cause of cancer-related death. Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer. Many patients developed into advanced stage of the disease when first diagnosed. With the discovery of epidermal growth factor receptor (EGFR) mutation in lung cancer, targeted therapy become an important strategy for advanced NSCLC. It significantly prolonged the patients' survival. Although first-, second- and third-generation of EGFR-tyrosine kinase inhibitors (TKI) have been successively developed and prescribed, patients eventually get drug resistance and disease progression as time goes on. In order to overcome this difficulty, relevant treatment strategies based on drug resistance mechanisms are under study. This review aims to summarize the research progress of EGFR-TKIs resistance mechanisms and treatment strategies in recent years, especially of the third-generation EGFR-TKIs, which are preferentially recommended in guidelines for its efficacy and safety.