Oral squamous cell carcinomas (OSCCs) have the potential for rapid and unlimited growth. Therefore, hypoxic tissue areas are common in these malignant tumours and contribute to cancer progression, resistance to therapy and poor outcome. Out of all proteins induced by hypoxia, hypoxia-inducible factors (HIFs) and their target genes have been most extensively studied. HIF1 is a heterodimeric transcriptional complex that functions as the main regulator of systemic and cellular oxygen homeostasis; it is composed of HIF1α and HF1β subunits. At physiological concentrations of oxygen, prolyl hydroxylases (PHDs) modify HIF1α and prepare it for proteasomal degradation. In hypoxia, PHDs are inhibited and HIF1α dimerises with HIF1β to form HIF1, which is responsible for the activation of several genes involved in multiple aspects of tumor biology. Among these genes, vascular endothelial growth factor (VEGF) is essential as a regulatory gene of angiogenesis in the adaptation to a hypoxic microenvironment. Previous studies have shown the correlation between HIF1α and VEGF in OSCC and high levels of HIF1α expression appear to predict a poor prognosis. The purpose of the present article is to review the hypoxic condition in OSCC and its correlation with prognosis.