Objective To investigate the effect of Xihuang Pill on vasculogenic mimicry（VM） of gastric cancer MGC-803 cells in tumor-bearing mice by regulating HIF-1α.Methods BALB/c nude mice were randomly divided into four groups by numerical table method after tumor bearing modeling: Blank control group, Xihuang Pill group, 2-ME group, Xihuang Pill+2-ME combination group, 6 mice in each group, and they were given corresponding intervention measures for 14 days respectively.Tumor volume of mice in each group was measured and calculated, mice were killed with their necks removed, and tumor tissues were collected from each group.The mRNA expressions of VE-cadherin, EphA2,MMP-2 and HIF-1α were detected by RT-qPCR,the protein expressions of VE-cadherin, EphA2,p-EPHA2 and MMP-2 were detected by immunohistochemistry, and the protein expression of HIF-1α was detected by Western-blot.Results Xihuang Pill could inhibit the proliferation of gastric cancer cells and decrease the volume and mass of gastric cancer cells（P<0.05）,decrease the number of VM formation in gastric cancer tissues, decrease the mRNA expression of VE-cadherin and MMP-2（P<0.01） and protein expression（P<0.05）,inhibit the phosphorylation of EPHA2（P<0.05）,and reduce the expression of HIF-1α protein and mRNA,the key factor of hypoxia（P<0.01）.Conclusion Xihuang Pill can inhibit the VM formation of gastric cancer MGC803 cells by regulating HIF-1α.