Introduction: oral squamous cell carcinoma (OSCC) is a major health problem in our country. the increasing incidence of youth dependence on tobacco , pan masala and gutka, which are known pre disposing factors have further aggravated the problem. Intra tumoral hypoxia activates a number of adapting pathways such as the Hypoxia Inducible Factor–1 α (HIF–1 α) which confers a survival advantage to the tumour cells. The present study was carried out to evaluate the association of HIF–1 expression with disease aggressiveness. Material & Methods: The study comprised of 50 histologically proven cases of oral SCC and 50 healthy controls. The HIF –1 α levels were measured by commercially available ELISA in the blood samples. The data was analysed using SPSS software version 20. Results: The HIF–1α levels were found significantly higher in the patients with aggressive disease regarding the histological grading of differentiation and the stage at presentation. Conclusions: Our findings prove that higher HIF–1 α levels indicate advanced state of the disease and consequent poor prognosis.