Background Oral squamous cell carcinoma is a common problem among tobacco chewers and related products in developing countries like India. Histopathological examination evaluates and confirms the diagnosis of oral SCC. Clinical examination and molecular profiling by histopathological examination (HPE) are important prognostic tools used in clinical practice. Histopathological grade, depth of invasion, lymphovascular invasion, perineural invasion and necrosis are the factors routinely assessed in every case during clinical examination. Aim and objectives The present study aims to evaluate TP53 expression and correlate it with the histopathological parameters of oral squamous cell carcinoma. Materials and methods The present retrospective study was conducted in the histopathological section of the Department of Pathology, Atal Bihari Vajpayee Government Medical College, Vidisha, Madhya Pradesh. All the histopathologically diagnosed cases of oral squamous cell carcinoma from November 2023 to October 2024 were included in the study. The collected data were scored, and the immunopositivity of P53 was recorded and correlated with histopathological parameters. Results Oral SCC histopathology was reviewed retrospectively, and the association of histopathological features with P53 was discussed. A total number of 45 cases were included in the study. The most common age group was 41-50 years comprising 18 patients (40%), followed by the 31-40 years age group consisting of 12 patients (26%). According to histopathological parameters, they were graded, scored, and correlated with P53. A p-value <0.05 was considered statistically significant.  Conclusion The initiating step in the treatment of patients with precancerous or malignant diseases in the oral cavity is accurate and timely diagnosis. The histopathological examination of suspicious oral lesions is currently the gold standard for diagnosis. The correct interpretation of biopsy, along with clinical and molecular evaluations, improves the prognosis. This study focuses on the importance of reporting various histopathological parameters of oral SCC.