Aim : To investigate the association among the polymorphisms of the cytochrome P450 1A1 and 2E1 genes, smoking, drinking and the risk of prostate cancer (PCa) in a Han nationality population in Southern China. Methods : A case-control study including 225 PCa patients and 250 age-matched controls was conducted. The six polymorphic sites of the CYP 1A1 and CYP2E1 genes were analysed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) or allele-specific PCR technique using genomic DNA isolated from peripheral blood lymphocytes. Results : We found that the CYP1A1 Val/Val genotype significantly increased the risk for PCa (OR, 2.26; 95% CI, 1.09-4.68). In contrast, the CYP2E1 C1/C2 (OR, 0.67; 95% CI, 0.46-0.99) or C2/C2 genotype (OR, 0.31; 95% CI, 0.10-1.00) significantly decreased the risk. Furthermore, the individuals carrying the CYP1A1 Val allele and the CYP2E1 C1/C1 genotype showed the highest risk (OR, 2.50; 95% CI, 1.45-4.29). Though there was no significant difference with smoking history ( P = 0.237) or drinking habit ( P = 0.499) between cases and controls, a deep smoking habit (OR, 2.02; 95% CI, 1.28-3.17) and heavy smoking history (OR, 1.61; 95% CI, 1.04-2.50) significantly increased the susceptibility of PCa after stratification by smoking method and accumulative smoking amount. Moreover, both the CYP1A1 Val allele (OR, 2.82; 95% CI, 1.49-5.35) and CYP2E1 C1/C1 genotype (OR, 2.57; 95% CI, 1.31-5.02) had obvious interaction with heavy smoking history that significantly raised the risk. We also discovered a significant interaction between the CYP2E1 C1/C1 genotype and drinking (OR, 1.85; 95% CI, 1.04-3.28). Conclusions : Individuals carrying the CYP1A1 Val allele or the CYP2E1 C1/C1 genotype with a smoking or drinking habit were at increased risk of PCa, which also showed a positive correlation with exposure dose of tobacco.