Background & Aims:The aim of this study was to evaluate serum lipid profile and compare their levels between the patients with oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC). Materials & Methods:This descriptive study was done in two groups of patients; OSMF and OSCC patients.There were forty-five participants in each group.Serum samples obtained from centrifugation of 12 hour fasting blood samples was analyzed by fully automated analyzer Beckman coulter AU-680 for estimation of the lipid levels (cholesterol, triglycerides (TGL), and high-density lipids (HDL)) using colorimetric methods.Low-density lipid (LDL) values were obtained by calculation.Results: The comparison of lipid profile between Oral Submucous Fibrosis and Oral Carcinoma cases shows statistically significant results for TC, HDL and LDL. Conclusion:The change in lipid levels may have an early diagnostic or prognostic role in oral premalignant and malignant lesions.