Abstract: Background : „Oral submucous fibrosis” (OSF) is chronic, progressive, and irreversible disease but also as oral potentially malignant disorder with high probability of malignant transformation. From a clinical as well as the histological point of view it appears to be of major importance to establish and understand the molecular nature of the mechanism of malignant transformation in OSF .So that these molecules could be targeted to formulate a standard treatment for high risk cases of OSF patients in need for better prognosis. Material and Methods: 25 Cases of “oral submucous fibrosis .” and 25 Cases of oral Submucous Fibrosis with coexisting oral squamous cell carcinoma will be analyzed.4 μm thick sections of formalin fixed paraffin embedded blocks were immunohistochemical stained with Polyclonal rabbit MT-1 MMP antibody , Monoclonal mouse TIMP-1 antibody ,Monoclonal mouse TGF-β1antibody , Monoclonal mouse α-SMA antibody in each case Statistical Analysis: Sample size formula based on difference between two proportions: This study uses the following formula for the sample size n: n = (Zα/2+Zβ) 2 * (p1(1- p1)+p2(1-p2)) / (p1-p2) 2 , Discussion: The Incidence of malignant potential in OSF has been estimated to be 7-13%². After years of persistent efforts and research, satisfactory and definitive treatment modality still eludes us. These markers could be used on regular basis to assess malignant potential of OSMF. This will help to formulate and decide the standard treatment plan with a better regime of target drug therapy.