Introduction: OSMF in India has been attributed to the increased consumption of areca nut. OSMF is a chronic disease of the oral cavity which is characterized by an epithelial and sub-epithelial inflammatory reaction followed by fibro elastic changes in the mucosa. Materials & Methods: The present study was aimed to estimate serum lipid profile i.e. TC, TG, (HDL-C), (LDL-C), (VLDL-C) in Moderate OSMF and compared with controls. The study subjects were divided into 2 groups i.e. Group-I (Moderate Oral Submucous Fibrosis), Group-II (controls). Group-I includes n = 50 patients of clin. diagnosed and histopathol. proven of Moderate Oral Submucous Fibrosis. They were in the age group of 20-45 years. Group-II (controls) were age and sex-matched, apparently healthy volunteers (n = 50) were included in this study. Serum lipid profile was analyzed in all study subjects using fully automated Clin. Chem. analyzer Siemens ADVIA 2400. Results: The present study shown statistically significant decreased serum levels of (TC), Triglycerides (TG), High D. Lipoprotein Cholesterol (HDL-C), Low D. Lipoprotein Cholesterol (LDL-C) and Very Low D. Lipoprotein Cholesterol (VLDL-C) levels in group-I when compared with group-II. Conclusion: The results of the present study showed that there is an inverse relationship between lipid profile and the presence of OSMF. The changes in lipid profile have long been associated with cancer because lipids play a key role in maintenance of cell integrity.