Long-term and heavy use of tobacco and tobacco products increases the risk of oral cancer. Indeed, approximately 75% of people with oral cancer have been found to use tobacco. The risk of oral cancer increases with the amount and duration of tobacco use. Excessive alcohol consumption, excessive sun exposure, being over 40 years old, and obesity also increase the risk of oral cancer. Individuals with a history of head and neck cancers have a higher risk of developing oral cancer, especially if they continue to smoke and drink alcohol. In addition, HPV infection, ultraviolet radiation, poor nutrition, a weakened immune system, having certain health conditions such as graft-versus-host disease or Fanconi anemia, and poor oral hygiene are also risk factors for oral cancer.

People with oral cancer have a higher likelihood of developing cancers of the larynx, esophagus, or lung.