BACKGROUND: lack of medical practitioners' knowledge about oral cancer has contributed to delays in referral and treatment. Oral cancer is amenable to treatment when detected early, which leads to better prognosis and survival rates. In this study, we aimed to assess the knowledge of the Syrian medical students about the risk factors of oral cancer, oral cavity changes associated with oral cancer, and the relation between the relation with Human Papilloma Virus (HPV) and oral cancer. METHODS: This is a cross-sectional study conducted at the Syrian Private University. Data were collected through self-administered questionnaires, which targeted social demographic information, general knowledge, risk factors, oral changes and HPV knowledge associated with oral cancer. Data was categorized and analyzed to assess and compare the levels of knowledge between clinical and preclinical students. RESULTS: 301 out of 401 medical students responded to the questionnaires bringing the response rate to 75.25%. The study revealed adequate knowledge about oral cancer, general information, clinical features, risk factors and relation to HPV. Clinical students showed higher levels of awareness compared to pre-clinical students. No significance in knowledge was found between the genders. CONCLUSION: The findings of the present study suggest that there is a need to reinforce the medical curriculum concerning oral cancer education, particularly in prevention and early detection to improve practices.