OBJECTIVE@#To investigate the effect and mechanism of inhibitor everolimus on EGFR-TKI resistance NSCLC.@*METHODS@#MTT assay was used to detect proliferation of humannon-small cell lung cancercell line A549. Flow cytometry was used to detect the changes of apoptosis and cycle distribution in each group after 24 h and 48 h. RT-PCR was used to detect the changes of PTEN and 4EBP1 expression levels after 48 h of monotherapy and combination therapy.@*RESULTS@#MTT assay showed that everolimus had dose-dependent inhibition against growth of A549 cells. Flow cytometry showed when everolimus could induce apoptosis and induce G0/G1 phasecell cycle arrest, which was time-dependent (P<0.05). RT-PCR showed everolimus could increase PTEN and 4EBP1 expression.@*CONCLUSIONS@#mTOR inhibitor everolimus has an inhibitory effect on EGFR-TKI resistant NSCLC, which cannot reverse the resistance effect of EGFR-TKI resistant cell line A549. The relationship between EGFR/AKT signaling pathway and the mTOR signaling pathway and the mechanism in non-small cell lung cancer need further study.