The objective was to examine the role of tobacco smoking and alcohol drinking in the incidence of oral cavity cancer by subsite in France, a high-incidence area. We analysed detailed data on lifelong tobacco smoking and alcohol drinking from 772 oral cavity cancer cases and 3555 controls included in a population-based case-control study, the ICARE study. Tobacco smoking increased the risk of oral cavity cancer even for the smaller quantities and durations, whereas alcohol drinking increased this risk only in heavy drinkers who were also ever smokers. The combined effect of smoking and drinking was greater than multiplicative. The floor of the mouth was the subsite that was the most affected by the harmful effects of tobacco and alcohol, whereas the gums were less susceptible.