The innovation points of this study are as follows: (1) NSCLC cell lines resistant to first-generation EGFR-TKI with different genetic mutation background were used as the research subjects to compare the differences in cytotoxicity, apoptosis and expression of important transduction signal factors between combined inhibition of upstream pathway (EGFR/MET) and combined inhibition of downstream pathway (MEK/PI3K). This evidence concerns the gene EGFR and non-small cell lung carcinoma.