Although the association for esophageal cancer with tobacco smoking and alcohol drinking has been well established, the risk appears to be less strong in China. To provide more evidence on the effect of smoking and alcohol consumption with esophageal cancer in China, particularly among Chinese women, a population-based case-control study has been conducted in Jiangsu, China, from 2003 to 2007. A total of 1,520 cases and 3,879 controls were recruited. Unconditional multivariate logistic regression analysis was applied. Results showed that the odds ratio (OR) and confidence interval (CI) for ever smoking and alcohol drinking were 1.57 (95% CI: 1.34-1.83) and 1.50 (95% CI: 1.29-1.74). Dose-response relationships were observed with increased intensity and longer duration of smoking/drinking. Risk of smoking and alcohol drinking at the highest joint level was 7.32 (95% CI: 4.58-11.7), when compared to those never smoked and never drank alcohol. Stratifying by genders, smoking and alcohol drinking increased the risk among men with an OR of 1.74 (95% CI: 1.44-2.09) and 1.76 (95% CI: 1.48-2.09); however, neither smoking nor alcohol consumption showed a significant association among women. In conclusion, smoking and alcohol drinking were associated with esophageal cancer risk among Chinese men, but not among Chinese women.