This study reviews the association between alcohol, tobacco, and the risk of cancers of the upper digestive and respiratory tract (i.e. oral cavity and pharynx, larynx, and esophagus) and liver. Alcohol drinking and tobacco smoking are the major risk factors for upper aerodigestive tract cancers, accounting for a large proportion (i.e. about three-quarters) of cases in developed countries. Consumption amount is the strongest alcohol-related determinant of risk, whereas the pattern of alcohol-related risk with duration is inconsistent. Both dose and duration of smoking have important effects on the risk of upper aerodigestive tract cancers. The combined exposure to alcohol and tobacco has a multiplicative effect on carcinogenesis of this tract. Alcohol and tobacco consumption are also causally related to liver cancer, although the associations are moderate and a lower fraction of neoplasms is attributable to these factors as compared with cancers of the upper aerodigestive tract. An interaction between alcohol drinking and tobacco smoking has been reported, but the issue is not adequately assessed.