Increased oxidative stress and altered anti-oxidant defense systems have been implicated in the pathogenesis of several diseases including cancer. Therefore, the aim of our study is to evaluate the antioxidant enzyme levels such as superoxide dismutase (SOD) and catalase in blood samples and tissues collected from oral squamous cell carcinoma patients and compared with healthy controls.The collected blood samples and tumor tissues from the diseased individuals and the normal controls are analyzed for malondialdehyde (MDA) and nitric oxide (NO), which is the indicator of oxidative and nitrosative stress respectively. The anti-oxidant enzymes SOD and catalase levels are measured by UV visible spectrophotometer. Subsequently, immuno-histostaining for antioxidant enzymes were performed in oral squamous cell carcinoma biopsies and sections were analyzed.The levels of MDA and NO were significantly elevated in the blood and tissue samples of OSCC patients. The antioxidant enzymes SOD and catalase were significantly reduced in OSCC tissues; while in erythrocytes catalase level is reduced whereas the SOD level is increased. Further, the reduced immuno-histostaining was observed for catalase and SOD in OSCC tissues when compared to normal oral epithelium.The enhanced levels of MDA and NO revealed that increased oxidative stress in conjunction with the reduced antioxidant defense mechanism in OSCC patients, might be involved in cancer progression. Our results suggest that detection of reactive oxygen species (ROS) and antioxidant enzymes levels might be a valuable marker in cancer prognosis and for improving therapeutic strategies in oral cancer.