Objective: To investigate the effect of hypoxia-induced factor 1α (HIF-1α) gene silence on the expression of vasculogenic mimicry associated genes in human esophageal squamous cancer. Methods:Eca109 cells were divided into normal control group(non-transfection group),negative control group(transfected with empty plasmid) and experimental group(stably transfected with recombinant plasmid pGCsi-shHIF-1α), and were transplanted into nude mice to establish esophageal squamous cancer-bearing nude mice. The growth of transplanted tumor in nude mice were observed. HE staining was conducted to detect atypia and necrosis of tumors in each group. Immunohistochemistry and Western blot were used to observe the protein expression of HIF-1α and epithelial kinase (EPHA2), vascular endothelial cadherin(VE-cadherin), matrix metalloproteinase-2 (MMP-2) in tumor tissue. RT-PCR was adopted to detect the mRNA expression of HIF-1α,EPHA2,VE-cadherin and MMP-2. Results:The tumor formation and growth in experimental group were lower than the control groups. The volume and weight were decreased significantly than the control groups(P < 0.05). HE staining confirmed the significantly decreased atypia and increased necrosis in experimental group. Immunohistochemistry and Western blot results showed that HIF-1α protein expression of the experimental group was silenced, and EPHA2, VE-cadherin expression were decreased significantly (P < 0.05). RT-PCR results suggested that the mRNA levels of HIF-1α and EPHA2, VE-cadherin, MMP2 in experimental group were decreased to a different extent, EPHA2 and VE-cadherin were significantly reduced(P < 0.05). Conclusion:HIF-1α gene silence can suppress the growth of esophageal squamous cancer in vivo and inhibit the VE-cadherin and EPHA2 expression in the formation of vasculogenic mimicry,HIF-1α may participate in the regulation of vasculogenic mimicry through these two sites in esophageal squamous cancer.