Abstract: Objective To explore the role of NS-398 on MVD and VEGF、MMP-9 expression of hepatocullar carcinoma. Methods VEGF and MMP-9 expressions were detected by RT-PCR and flow cytometry. Microvascular density of xenograft tissue were detected by immunohistochemical staining and the serum PGE2 was detected by ELISA. Results The expressions of VEGF and MMP-9 were significantly downregulated in SMMC-7721 cells exposed to NS-398 in a dose-dependence and time-dependent manner (P<0.001). Expression of VEGF, MMP-9 mRNA and protein in xenografts treated with NS-398 were lower than those of control group (P<0.001). The density of microvessel was notably lower in xenografts treated with NS-398 than in those without treatment and serum PGs level was also significantly lower than in those without treatment (P<0.001). Conclusions Expression of COX-2 contributes to angiogenesis in hepatocullar carcinoma. NS-398 may suppress angiogenesis of hepatocellular carcinoma cell via reducing expressions of VEGF and MMP-9.