Objective To investigate the association between alcohol drinking, tobacoo smoking and oral cancer. Methods We conducted a case-control study with 206 cases and 584 population-based controls. Patients were recruited from the First Clinical Medical College with pathologic confirmation. Control subjects were enrolled from hospital visitors and community population. Eligible participants were personally interviewed using a questionnaire. Unconditional logistic regression model and single factor analysis was performed to calculate to alcohol drinking and oral cancer risk odds ratios(ORs)and 95% confidence intervals(CIs), and to analysis the interaction of alcohol drinking and smoking. Results Alcohol drinking can significantly increase the risk of oral cancer, ORs and CIs were 2.06(95% CI: 1.33～3.01). As the earlier start drinking age, the increasion of average alcohol consumption one day, the extension of drinking years, drinkers increase risk of oral cancer. Among them, drinkers who one day on average alcohol consumption more than 60 g has significant correlation on oral cancer(P<0.05), ORs were 5.98(95% CI: 3.26～10.95); The risk of oral cancer with both smoking and drinking were 4.77 times more than one neither smoking nor drinking(95% CI:2.71～8.39). Using Logistic regression model, the ORs were 3.58(95% CI:2.45～5.24)of cross-product term of smoking and drinking. Adjusted RERI, AP and S were 2.87(95% CI: 0.73～5.02), 0.60(95% CI: 0.33～0.87), 4.20(95% CI: 0.95～18.66). Alcohol drinking have multiplication and addition interaction with smoking, they could increase the risk of oral cancer. Conclusions There is synergistic effect between drinking and smoking, they could increase the risk of oral cancer.