The aim of this study was to evaluate the levels of lipid peroxidation and antioxidants in the erythrocytes of oral cancer patients and tobacco chewers/smokers. 25 patients with biopsy proven oral squamous cell carcinoma(OSCC), 25 cases of tobacco chewers/smokers and 25 age and sex matched healthy control subjects were included in the study. The levels of malondialdehyde (MDA), a lipid peroxidation marker and antioxidants like superoxide dis-mutase(SOD) and glutathione(G-SH) were determined by colorimetric methods. Erythro-cyte MDA levels were significantly increased (p<0.001) and erythrocyte SOD and G-SH lev-els were significantly reduced (p<0.001) in OSCC patients compared to control subjects, where as statistically significant increase(p<0.05) in SOD was observed in tobacco chew-ers/smokers group. There is a negative correlation between MDA and G-SH in OSCC pa-tients and tobacco chewers/smokers. This study shows that there is higher magnitude of oxidative stress in OSCC patients and a weak antioxidant defense system makes the muco-sal cells more vulnerable to the genotoxic effect of reactive oxygen species(ROS). A diet rich in antioxidants may alleviate the oxidative stress to some extent.