Summary: This study aims to find good markers for predicting the prognosis of patients with eso- phageal squamous cell carcinoma (ESCC). Vasculogenic mimicry (VM) and the expression of hy- poxia inducible factor-1α(HIF-1α)/E-cad protein in ESCC were investigated by immunostaining. The association between VM, HIF-1α/E-cad and clinicopathologic characteristics and 5-year-survival rate of patients with ESCC was analyzed. A total of 160 ESCC specimens were involved in this study and 28 specimens of normal esophageal mucosa served as controls. VM channels were identified in 78 (48.75%) of the 160 ESCC specimens and none of the normal esophageal mucosa was found to have VM. The rates of high-expression of HIF-1αand E-cad in ESCC were 43.75% and 38.75%, while the rates in control were 17.86% and 71.43%, respectively (P〈0.05 for all). VM and the expression levels of HIF-1α and E-cad were significantly related to lymph node metastasis, serosa infiltration, PTNM staging and 5-year-survival rates of patients with ESCC (P〈0.05 for all). VM was positively corre- lated with HIF-1α but negatively with E-cad, and HIF-let was negatively correlated with E-cad (P〈0.001 for all). The 5-year-survival rate of patients with ESCC was 6.41% (5/78) in VM group and 65% (52/82) in non-VM group, 7.14% (5/70) in high HIF-1α expression group and 57.78% (52/90) in low HIF-1α expression group. Oppositely, the 5-year-survival rate in high E-cad expression group was 80.65% (50/62) and that in low E-cad expression group was 7.37% (7/98) (P〈0.05 for all). Cox multifactor regression analysis indicated that lymph node metastasis, PTNM stage, VM and expres- sion levels of HIF-1α and E-cad were independent risk factors of patients with ESCC (P〈0.05 for all). Combined detection ofVM, HIF-1α and E-cad plays an important role in predicting the invasion, me- tastasis and prognosis of patients with ESCC.