AIM: To evaluate the impact of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2)polymorphisms on esophageal cancer risk.METHODS: One hundred and ninety-one esophageal cancer patients and 198 healthy controls from Yanting County were enrolled in this study. ADH2 and ALDH2genotypes were examined by polymerase-chain-reaction with the confronting-two-pair-primer (PCR-CTPP)method. Unconditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence interval (95% CI).RESULTS: Both ,ADH2*1 allele and ,ALDH2*1/*2 allele showed an increased risk of developing esophageal cancer. The adjusted OR (95% CI) for ,ADH2*1allele compared with ,ADH2*2/*2 was 1.65 (95%CI= 1.02-2.68) and 1.67 (95% CI= 1.02-2.72) for ,ALDH2*1/*2 compared with ALDH2*1/*1. A significant interaction between ,ALDH2 and drinking was detected regarding esophageal cancer risk, the OR was 1.83(95% CI = 1.13-2.95). Furthermore, when compared with ADH2*2/*2 and ALDH2*1/*1 carriers, ADH2*1 and ALDH2*2 carriers showed an elevated risk of developing esophageal cancer among non-alcohol drinkers (OR =2.46, 95% CI= 0.98-6.14), and a significantly elevated risk of developing esophageal cancer among alcohol drinkers among alcohol drinkers (OR = 9.86, 95% CI=3.10-31.38).CONCLUSION: ADH2 and ALDH2 genotypes are associated with esophageal cancer risk. ADH2*1 allele and ALDH2*2 allele carriers have a much higher risk of developing esophageal cancer, especially among alcohol drinkers.