Background: Squamous Cell Carcinoma (SCC) is a type of cancer that is often found in oral cavity and areas of the head and neck. Viruses are major etiological factors through production of factors that can disturb proliferation and apoptosis regulators such as p53i, c-myc and bcl-2. This study aimed to determine the molecular grading of oral squamous cell carcinoma (OSCCs) infected with the Epstein-Barr Virus (EBV). Methods: Twenty-seven OSCC patients underwent biopsy to detect EBV infection through in situ hybridization for RNA EBV (EBER) and immunohistochemical analysis of latent membrane protein-1 (LMP-1) and EBV nuclear antigen-1 (EBNA-1). To assess molecular grades, cell proliferation and apoptosis regulator expression i.e. inactive p53 (p53i), c-myc and bcl-2, were immunohistochemically analysed. Results: The cases were divided into two groups; infected and non-infected by EBV. Regression analysis showed that only EBNA-1 expression could affect p53i expression. Based on regression equations molecular grading of OSCCs infected by EBV was divided into three: Grade I (low), EBNA-1 expression was 7.60, and p53i expression was 9.74-17.5; Grade II (medium), EBNA-1 expression was 7.61-19.7, and p53i 17.5-30.1; Grade III (high), EBNA-1 expression was 19.71, and p53i ≥ 30.1. Conclusion: In OSCC infected with EBV, only EBNA-1 expression can influence p53i expression.