Objective: This study aimed to analyze the status of human papillomavirus (HPV) infection status and p53 expression in Indonesian patients with oral squamous cell carcinoma (OSCC) and their relationship with patient survival. Methods: This retrospective cohort study was conducted in Indonesia's main referral hospital with 74 patients diagnosed with OSCC between January 2014 and December 2018. Polymerase chain reaction followed by hybridization was performed to detect HPV genotypes in tumor tissues. The expression of p53 was assessed by immunohistochemistry. Clinicopathological data were collected and patients were followed up for a minimum of 36 months from the month of diagnosis. Statistical tests and survival analyses were also performed. Results: HPV infection was identified in 52 (70.3 %) patients, mostly out-panel genotypes of HPV followed by HPV35. There were no differences in the clinicopathological characteristics between HPV-positive and HPV-negative patients. Positive p53 expression was observed in 47 (63.5 %) patients. The p53-negative patients were significantly younger than the p53-positive patients. No difference in 3-year overall survival was observed between patients with OSCC stratified by HPV infection status and p53 expression. Univariate and multivariate analyses showed that HPV infection status and p53 expression did not correlate with survival. Conclusion: HPV infection and p53 expression were not suitable as prognostic markers for survival in our patients due to the lack of significant associations. © 2025 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI