Introduction: Oral cancer ranks sixth place worldwide among other cancers and is known for its high morbidity and mortality rates. Among oral cancer, oral squamous cell carcinomas (OSCC) remains the most common. Expression of specific biomarkers are known to be related to the prognosis of the OSCC. Methodology: An immunohistochemistry study was performed to evaluate the expression of Cyclin D1 and CENPF for their prognostic significance in twenty OSCC patients. The follow-up period ranged from 10 to 18 months. The expression of these proliferative markers was correlated with demographic, clinical and histopathological grade of the disease. Results: The results revealed 28% mortality rates in relation to OSCC involving retro-molar trigone. Based on the Cyclin D1 and CENPF expression, high mortality rate (Pearson coefficient = 0.800) was seen with grade 3 and 4 expressions of the markers. Decreased survival rates (Pearson coefficient = 0.824) were observed with stage III and IV disease with grade 3 and 4 expressions of the markers. Conclusion: Cyclin D1 and CENPF have shown promising results as proliferative markers which can be linked with prognosis of OSCC in this study. Further studies with larger sample size are needed to extrapolate our findings. © 2023 Elsevier B.V., All rights reserved.