Objective: To study the relationship between genetic polymorphism of cytochromes P4502E1 RsaⅠand smoking,alcohol drinking habit with the susceptibility of rectal cancer. Methods:A case-control study was conducted with 210 cases of rectal cancer and 439 population-based controls in Jiangsu Province, China. The epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all the subjects. CYP2E1 RsaⅠgenotypes were detected by PCR-RFLP. Results:The frequencies of CYP2E1 RsaⅠ c1／c1,c1／c2 and c2／c2 genotypes were 58.4%, 34.0% and 7.7% in rectal caner cases, compared with 61.4%, 35.6% and 3.0% in controls（χ2 = 7.07, P = 0.029）. Individuals with CYP2E1 RsaⅠ c2／c2 genotype were at an increased risk of rectal cancer（adjusted for age, sex and status of the smoking and alcohol drinking，OR = 1.64, 95% CI:1.12-2.41） compared with those with CYP2E1 RsaⅠ c1／c1 genotype. Individuals who had alcohol drinking habit were at an increased risk of rectal cancer（adjusted OR = 2.08, 95% CI:1.36-3.19）, whereas smoking was not associated with risk of rectal cancer. There was a significantly cooperated effect between CYP2E1 RsaⅠ polymorphism and alcohol drinking habit in the risk of rectal cancer. The risk of rectal cancer of individuals with CYP2E1 RsaⅠ c2／c2 genotypes and drinking habit increased 5.75 times（95%CI：1.65-20.05）. Conclusion：Polymorphisms of the CYP2E1 RsaⅠ and acohol drinking have effects on rectal cancer and have significantly synergic effect.