Oral Squamous Cell Carcinoma (OSCC) is the most common malignancy of the oral cavity and accounts for nearly 90% of all oral cancers. Traditionally, tobacco use, alcohol consumption, and betel nut chewing have been recognized as the primary etiological factors. However, increasing evidence suggests that Human Papillomavirus (HPV), particularly high-risk HPV genotypes such as HPV-16 and HPV-18, plays a significant role in the development of a subset of oral and oropharyngeal cancers. HPV-associated carcinogenesis involves viral oncogene expression, disruption of cell cycle regulation, genomic instability, and immune evasion. This review examines the role of HPV in OSCC, including epidemiology, molecular mechanisms, diagnostic approaches, clinical characteristics, prognosis, prevention strategies, and future research directions. The findings indicate that HPV-positive OSCC demonstrates distinct biological behavior and may have different therapeutic and prognostic implications compared with HPV-negative tumors. Understanding HPV's role in oral carcinogenesis is essential for improving early diagnosis, targeted therapies, and preventive interventions.