Objective To explore the characteristics and biological functions of epigenetic treatment to DNMT1 expression in NSCLC cell lines. Methods Lung cancer cells were divided into 4 groups , and drugs with different concentrations. The effect of epigenetic treatment on NSCLC cell line was detected by CCK-8 and MTT. The effect of epigenetic treatment on the expression of DNMT1 in NSCLC cell line was detected by Western blot. Results CCK-8 and MTT assay showed that treatment with 5-Aza-CdR and MS-275 inhibited the proliferation of NSCLC cells. Western blot showed that treatment with 5-Aza-CdR and MS-275 inhibited the DNMT1 expression in NSCLC cells. Conclusion The expression of DNMT1 gene in the NSCLC cell lines may be suppressed effectively by epigenetic treatment , and the gene may inhibit the proliferation and growth of NSCLC cell lines.