Oral cancers are among the 10 most common causes of cancer-related deaths in the world. The etiology appears to be multifactorial and strongly related to lifestyle, mostly habits, and diet (particularly tobacco alone or in betel, and alcohol use), although other factors as immune defects or immunosuppression, defects of carcinogen metabolism, or defects in DNA-repair enzymes may be implicated. Here, LIG4 is linked to cancer.