Objective To study the relationship between polymorphisms of NQO1 and hepatocellular carcinoma (HCC) in Zhengzhou and Guilin area.Methods The Zhengzhou group was a hospital-based case-control study which included 146 cases of HCC and 151 cases of controls with nontumor seen in the People's Hospital of Zhengzhou.The Guilin group was a hospital-based case-control study which included 136 cases of HCC and 123 cases of controls with non-tumor seen in the Guilin Medical University Hospital.NQO1 polymorphisms were determined by polymerase chain restriction with TaqMan MGB probe.All data were analyzed by conditional logistic multiple factor regression analysis with SPSS 18.0 statistical package.Results The frequency with mutation allele (T) in the case group was significantly different between the Zhengzhou and Guilin groups (x2=23.307,P＜ 0.05).The odds risk of NQO1 mutation homozygote and mutation heterozygote to wild homozygote were significantly increased (OR=2.476,CI:1.518～4.038).Conclusions NQO1 mutation genotype is the predisposing gene with relatively different susceptibility to the development of HCC in the Zhengzhou and Guilin regions.There are synergistic effects between the NQO1 predisposing genotype,drinking and smoking.