Oral cancer, a complex multistage process, is predominant in the Southeast Asian countries, owing to increased consumption of smokeless tobacco, tobacco, alcohol and Human papilloma virus type 16 infection. Oral cancers tends to advance from the non-healing pre-malignant lesions, namely, leukoplakia, erythroplakia and oral sub-mucous fibrosis. However, the major challenge encountered is to predict which pre-cancerous lesion might transform into oral carcinoma, indicating the importance of protein based molecular markers or biomarkers. Several biomarkers, with diagnostic, prognostic and therapeutic value for oral carcinogenesis have been identified till date and this review focuses on the current understanding of the potential OSCC biomarkers, such as Endothelin 1, salivary transferrin, zinc finger protein 510, microRNA: miR-31 as well as cytokine biomarkers, including