Introduction: Oral squamous cell carcinoma (OSCC) is the most common cancer in the oral cavity. It accounts for more than 90% of all oral cancer. Tobacco use is a major risk factor for many chronic diseases including cancers, Cardiovascular diseses, lung diseases and stroke. AIM: This study was conducted to compare the efficacy of Toluidine blue and Acetic acid in detection of Oral Squamous Cell Carcinoma and to evaluate the association of these two tests with expression of tumor marker p53.Materials & Methods: A total of 50 patients were included in study 25 patients underwent acetic acid test while other 25 underwent toluidine blue test. All the 50 patients underwent histopathological and immunohistochemical investigation of lesion for p53.