Abstract: Acquired resistance to EGFR-TKI after a period of time has become a puzzle in clinic treatment. This review introduced the mechanism of acquired resistance to EGFR-TKI and focused on the recent discovered treatments after TKI resistance, including pan-HER TKI, EGFR-VEGFR double inhibition，C-MET inhibitor, PTEN activator and new drugs targeting EGFR mutation.

Key words: epidermal growth factor receptor- tyrosine kinase inhibitors, drug resistance, therapeutic strategies