Abstract: Objective To explore inhibitory effects of S-adenosylmethionine on vascular endothelial growth factor-C (VEGF-C) protein and cellular proliferation in gastric cancer by regulating methylation status of VEGF-C promoter. Methods MTT analyses and nude mice model were employed to examine the effects of S-adenosylmethionine on inhibiting gastric cancer growth In vitro and in vitro The protein expression of VEGF-C in gastric cancer cells was assessed by Western blot. The methylation status of VEGF-C promoter was assessed by bisulfite genomic DNA sequencing analysis. Results VEGF-C promoter was hypomethylated in MGC803 and SGC7901. The treatment of S-adenosylmethionine resulted in a heavy hypermethylation of VEGF-C promoter, which consequently down regulated protein level of VEGF-C. S-adenosylmethionine effectively inhibited the growth of gastric cancer cells In vitro and in vitro (P<0.05). Conclusion S-adenosylmethionine can effectively reverse DNA hypomethylation on VEGF-C promoter which down-regulates VEGF-C protein expression and inhibit gastric cancer growth.