Aim: Alcohol dehydrogenase-IB (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) are the key enzymes for elimination of ethanol and acetaldehyde, the latter being an established animal carcinogen produced after drinking. In this study, we aimed to evaluate the contribution of ADH1B and ALDH2 polymorphisms to the risk of esophageal squamous cell (ESCC) in Chinese females. Methods: A total of 81 pathologically-proven female ESCC cases and 162 female controls were recruited from the Affiliated Hospital of Medical College of Armed Police Forces of PRC in China. ADH1B and ALDH2 polymorphisms were genotyped using PCR-CTPP. Results: Compared with those with ADH1B*2/*2, individuals with ADH2*1/*2 and ADH2*1/*1 had 1.47 and 2.36-fold, respectively, increased risk of developing ESCC (95%CI=0.84-2.58, 95%CI=1.14-5.79) after adjusting for alcohol consumption and other covariates. Significantly increased risk was also noted among subjects with ALDH2*1/*2 (adjusted OR=3.24, 95%CI=1.45-5.36), when compared to those with ALDH2*1/*1. Risk was greater in heavy drinking females carrying ADH1B *1/*1 or ALDH2*1/*2 genotypes compared to those with ADH1B*2 and ALDH2*1/*1. Moreover, we found a significant trend of ESCC risk with alcoholic consumption in women with ALDH2*1/*2. Conclusion: Chinese women with ADH1B *1/*1 or ALDH2*1/*2 have elevated risk of ESCC similarly to men. Women with inactive ADH1B and ALDH2 should reduce drinking and increase their intake of vegetable and fruit to prevent development of esophageal cancer.