Abstract: Objective To detect the expression of VEGF^_165band HIF-1α in esophageal squamous carcinoma tissues and their significance. Methods Immunohistochemistry SP method was used to detect the expression of VEGF_165b and HIF-1α in 143 cases of esophageal squamous carcinoma tissues. Results The positive expression rate of VEGF_165b and HIF-1α in esophageal squamous carcinoma tissues was 13.3% and 43.4% respectively; The expression rate of VEGF_165b showed a negative correlation with that of HIF-1α(P=0.035). Alcohol drinking was positively correlated with the expression rate of HIF-1α (P=0.027).The expression rate of HIF-1α showed a positive correlation with the depth of invasion, lymph node metastasis and pathologic grades. Conclusion The expression of VEGF_165b and HIF-1α played an important role in the development of esophageal squamous carcinoma, and the VEGF_165b、and HIF-1α may have a synergistic effect in the pathogenesis of esophageal carcinoma. Alcohol drinking was an important risk factor of esophageal carcinoma and VEGF_165b may be a potential therapy target.