Background: Hypoxia is a common feature of many cancers which contributes to local and systemic cancer progression and is associated with resistance to treatment. Hypoxia inducible factor-1α (HIF-1α) is a key regulator of the cellular response to hypoxia and it targets the transcription of over 60 genes. Vascular endothelial growth factor (VEGF) is one of the major HIF-1α target genes and also is one of the most potent stimulators of angiogenesis. The purpose of this study was to correlate the expression of HIF-1α and VEGF with grades of OSCC, and to clarify the correlation between the expression of HIF-1α and VEGF proteins Mateials and Methods: Twenty specimens in paraffin embedded tissue sections of OSCC were immunostained with HIF-1α and VEGF. Results: Expression of HIF-1α and VEGF was positively observed in all cases. There was a highly significant increase in HIF-1α and VEGF immunoreactivity from well to poorly differentiated OSCC (p<0.001). A significant correlation between HIF-1α and VEGF expression (p<0.001) was detected. Conclusion: These results suggest that HIF-1α and VEGF may serve as important indicators to evaluate the biological behavior of OSCC such as progression, metastasis and prognosis.