Abstract: Objective: To analyze the expression of hypoxia inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in esophageal squamous cell cancer (ESCC) and to examine the relationship between this expression and the curative effect of radiotherapy. Methods: The expression of HIF-1αand VEGF in 50 samples of ESCC was examined using SP immunohistochemical staining and was analyzed according to the clinicopathologic features and follow-up data. Results: The positive expression rate of HIF-1αand VEGF in ESCC was 68.0% and 74.0%, respectively. The positive rate of HIF-1αwas positively correlated with the presence of VEGF protein (r=0.391, P=0.005). The positive expression of HIF-1αwas closely related to clinical stage, prognosis and short-term effects of radiotherapy (P<0.05), but was not correlated with the pathologic type of the tumor or the size of the primary tumor (P>0.05). The 1-, 2-and 3-year survival rate of the patients with positive expression of HIF-1αwas 38.2%, 6.0%, 0.0%, respectively, while the 1-, 2-and 3-year survival rate of the patients with no detectable expression of HIF-1αwas 81.3%, 54.2%, 7.9%, respectively. The survival rate of the patients with positive expression was obviously lower compared to that of the patients with negative expression, and the difference was statistically significant (P<0.05). In patients with tumors positive for HIF-1α, the rate of favorable response to radiotherapy was 18.8%, and these patients had a median survival time of 10 months; in patients with tumors negative for HIF-1α, the rate of favorable response to radiotherapy was 81.3%, and these patients had a median survival time of 25 months. Conclusions: Overexpression of HIF-1αis found in ESCC. The expression of HIF-1αmay serve as an important parameter for evaluating the response to radiotherapy and establishing a prognosis for patients with ESCC. It may play an important role by upregulating transcription of the VEGF gene.