Introduction: Cancer has multifactorial aetiology and is a multistep process involving initiation, promotion and tumour progression. Cellular proliferation is one of the important indicators for the biologic aggressiveness of a malignant lesion. The dysregulated proliferation may be a significant change to determine the potential prognosis of various malignant tumours. Aim: The aim of this study was to evaluate the expression of proliferating cell nuclear antigen (PCNA) as an indicator for clinical aggressiveness in oral premalignancy and squamous cell carcinoma. Materials and Methods: A total of 50 blocks were taken from the Department of Oral Pathology which was diagnosed previously histopathologically. It comprised of normal oral mucosa (10), dysplasia (10) and grades of oral squamous cell carcinoma (30) of patients between the age group of 40-60 years. From each block, sections of 4 micro metre thicknesses were prepared and placed on poly-L lysine coated slides. These sections were immunohistochemically stained with monoclonal proliferating cell antibody (PC10). The stained slides were evaluated by a single examiner for cell count. Results: A comparison between study groups and controls showed a probability value (p-value) < 0.05. Significant increase in the proliferative index from the normal to oral squamous cell carcinoma was noticed. Poorly differentiated squamous cell carcinoma showed maximum proliferative index followed by moderately differentiated, well differentiated squamous cell carcinoma, dysplasia and normal mucosa. Conclusion: Present study concluded that PCNA index can be used to assess the proliferation and aggressiveness in dysplasia and different grades oral squamous cell carcinoma.