Objective To investigate the correlation between drinking behavior and polymorphism combination of extracel-lular superoxide dismutase (EC-SOD) and aldehyde dehydrogenase 2 (ALDH2) genes and oral squamous cell carcinoma.Methods The genetic polymorphisms of EC-SOD and ALDH2 were analyzed by polymorphism-polymerase chain reaction technique in peripheral blood leukocytes of 750 oral squamous cell carcinoma cases and 750 non-cancer controls.Results The frequencies of EC-SOD (C/G) and ALDH2 variant genotypes were 38.27% and 69.47% in oral squamous cell carcinoma cases and 21.07% and 44.40% in healthy controls, respectively. Statistical tests showed significant difference in the frequencies between the two groups (PConclusion EC-SOD (C/G) and ALDH2 variant genotypes and drinking are the risk factors in oral squamous cell carcinoma, which could carry out a coordinated attack of oral squamous cell carcinoma.