Abstract： Objective： To observe the inhibitory effect of different concentrations of Weifufang water extract (WFF) on the proliferation of human gastric cancer HGC- 27 cells， and to further explore the mechanism of the regulation of HIF- 1α/VEGF signaling pathway by WFF. Methods： Used different concentrations (1.2 mg/mL，1.3 mg/mL，1.4 mg/mL，1.5 mg/mL，1.6 mg/mL，1.7 mg/mL，1.8 mg/mL) of WFF. CCK-8 method was used to find the optimal intervention concentration and observe the effects of different intervention groups [non- specific control group (NC group)， WFF group， WFF + HIF- 1α overexpression plasmid group，WFF+2-MeOE2 (HIF-1α inhibitor) group，HIF-1α overexpression plasmid group， 2- MeOE2 group， Apatinib Mesylate group] on proliferation of HGC- 27 cells. Angiogenesis experiment was used to observe the effect of different groups on the angiogenesis ability of gastric cancer cells. Western blot method was used to observe the effects of different groups [NC group， WFF group， WFF+HIF-1α overexpression plasmid group，WFF+2-MeOE2 (HIF-1α inhibitor)，HIF-1α overexpression plasmid group，2- MeOE2 group] on the expression of HIF- 1α/VEGF signaling pathway- related proteins. Results：CCK-8 method verified that compared with NC group，WFF inhibited HGC-27 cell proliferation， the difference was significant (P＜0.01)， and it was dose- dependent. Compared with NC group， WFF group， WFF + HIF- 1α overexpression plasmid group， WFF + 2- MeOE2 (HIF- 1α inhibitor) group， 2- MeOE2 group，Apatinib Mesylate group had a statistically significant inhibitory effect on the proliferation of HGC- 27 cells，the difference was significant (P＜0.01). Compared with WFF group alone，the activity of cells in WFF + HIF- 1α overexpression plasmid group increased，the difference was statistically significant (P＜0.01)，and the activity in WFF + 2- MeOE2 group decreased，the difference was statistically significant (P＜0.01). Compared with HIF- 1α overexpression plasmid group， WFF + HIF- 1α overexpression plasmid group effectively inhibited the proliferation of HGC- 27 cells，the difference was statistically significant (P＜ 0.01). Compared with 2- MeOE2 group， WFF + 2- MeOE2 group effectively inhibited the proliferation of HGC- 27 cells， and the difference was statistically significant (P＜0.01). The angiogenesis experiment verified that WFF effectively reduced the angiogenesis capacity of human gastric cancer HGC- 27 cells， except HIF- 1α overexpression plasmid group， the other groups decreased the angiogenesis capacity of HGC- 27 cells compared with NC group， the difference was statistically significant (P＜0.05， P＜0.01). Compared with WFF group，the number of component tubes，crossing points，mesh number and length increased in WFF + HIF- 1α overexpression plasmid group (P＜0.01)， and the number of tubes， crossing points，mesh number and length decreased in WFF+2-MeOE2 group，and the difference was statistically significant (P＜0.01). Compared with HIF-1α overexpression plasmid group，WFF+HIF-1α overexpression plasmid group composition tube number， crossing points， mesh number and length decreased， the difference was statistically significant (P＜0.01). Compared with 2-MeOE2 group，the number of WFF+2- MeOE2 group component tubes，mesh number and length decreased，and the difference was statistically significant (P ＜ 0.01). Western blot verified that the WFF down- regulated the protein expressions of HIF- 1α， VEGFA， VEGFR- 2， Ki- 67 and PCNA (P＜0.05)， and had antagonistic and synergistic effects with HIF- 1α overexpression plasmid and 2- MeOE2， respectively. Conclusion： WFF may inhibit the proliferation and anti-angiogenesis of gastric cancer cells by inhibiting HIF-1α/VEGF signaling pathway.