Numerous studies indicate the importance of hypoxia-induced pathway in tumor angiogenesis, but in vivo studies examining the importance of this mechanism in prognosis of patients with head and neck squamous cell carcinoma present conflicting results. We performed a retrospective analysis of 81 patients with head and neck squamous cell carcinoma in order to investigate whether hypoxia-inducible factor 1a (HIF-1a) immunohistochemical expression correlates with vascular endothelial growth factor (VEGF) expression and clinicopathologic parameters or prognosis. Our results showed a statistically significant association between HIF-1a and VEGF expression in tumors located in the lower lip and in larynx, but not in those located in the oral cavity. HIF-1a expression had no impact on prognosis, while VEGF expression correlated significantly with adverse prognosis. These findings support the hypothesis that tumor angiogenesis is close related, but not strictly dependent, on the hypoxic conditions of tumor's microenvironment.