Objective:To examine the relationship between miR-200c promoter methylation and the response of non small cell lung cancer(NSCLC)cells to(TKI). Methods:NSCLC cell lines H1650,HCC827 with EGFR 19 deletion and cell lines H358 and H1299 with wild type EGFR were used in this study. The methylation of miR-200c promoter region was examined by methylation-specific PCR (MSP). The response of different cell lines to gefitinib was examined by cell counting kit-8 (CCK-8)assay. The expression of miR-200c was examined by RT-PCR. When treated with 5-aza-CdR,the response to gefitinib and miR-200c expression of four cell lines H1650,HCC827,H358 and H1299 were observed. Results:HCC827 and H358,which were sensitive to gefitinib,highly expressed miR-200c with promoter unmethylated. H1650 and H1299,which were insensitive to gefitinib,expressed low levels of miR-200c with promoter methylated. When treated with 5-aza-CdR,H1650 and H1299 expressed higher miR-200c and were more sensitive to gefitinib than before (P < 0.05),while HCC827 and H358 had no alteration in miR-200c expression and the sensibility to gefitinib(P > 0.05). Conclusion: As methylation of gene promoter suppressed the expression of miR-200c, the lung cancer cell lines H1650 and H1299 can be insensitive to gefitinib.