Aim and Objective: Comparison of IHC expression of P53 protein in frozen section versus routine paraffin embedded section in OSCC. Materials and Methods: Patients diagnosed with OSCC were selected from the Department Of Oral and Maxillofacial Surgery of Sharad Pawar Dental College, Sawangi,During curative surgery tissue sections were obtained for frozen IHC and paraffin embedded sections were obtained from routinely processed ressected tissue which were sent for histopathological diagnosis were also subjected to IHC for the purpose of the study. The tissue when then assessed to determine the expression of p53 protein. Results: Sharper and more extensive p53 protein expression was observed in frozen section as compared to formalin fixed paraffin embedded sections. This is thought to be due to the blockage of antigen sites by formalin. Conclusion: This study is of great significance to the pathologist who routinely assess IHC and reports on frozen section as diagnostic tools to guide the surgeon in order to determine the extent to which the ressection should be carried out. Hence, we can conclude that frozen section is more derivative in accordance with time as compared to formalin fixed tissue for determining the expression and as an important investigation to modify resection by using various tumor markers. In our study, we also considered conduction of IHC for margins during surgical procedure in order to guide the surgeon whether the margins are positive or negative and if the resection has to be extended or not. IHC here was conducted in a time period of 2 hours by polymer technique. Hence, an important and more definitive diagnostic tool for immediate results.