Objective:To explore the association between polymorphisms of NF-κB1 and NF-κBIα and the risk of hepatitis B virus-associated heptocellular carcinoma (HCC). Methods: The genetic polymorphisms of NF-κB1 and NF-κBIα were detected using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) in patients with the hepatitis B virus-associated HCC, patients with chronic hepatitis B and healthy controls. Multivariate Logistic regression model was used to assess the association of the age, sex, smoking history, alcohol drinking,and site of genetic polymorphisms with the susceptibility to HCC. Results: The frequency of NF-κB1 (ATTG2/ATTG2) genotype was significantly higher in HCC group than in healthy controls (odd ratio \[OR\] =2.21, 95% CI 1.25-3.88). Compared to the people who carried NF-κB1 (ATTG1/ATTG1) and NF-κBIα (AA) genotype spontaneously, healthy controls who carried NF-κB1 (ATTG2/ATTG2) and NF-κBIα (GG) genotype had an increased risk for HCC (OR=2.94, 95% CI 1.03-8.44). Chronic hepatitis B patients who carried NF-κB1 (ATTG2/ATTG2) genotype had an increased risk for HCC (OR=2.31, 95% CI 1.22-4.38). Multivariate analysis showed increased risk in male HCC patients with chronic hepatitis B(OR=2.01, 95% CI 1.19-3.41), in those who carried NF-κB1 (ATTG2/ATTG2) genotype (OR=2.17, 95%CI 1.23-3.85), in those who had a smoking history (OR=1.79, 95% CI 1.04-3.07), and in those who had a drinking history (OR=2.58, 95% CI 1.50-4.43). Conclusion: Genotype NF-κB1 (ATTG2/ATTG2) is a risk factor of HCC, and it has a synergistic effect with NF-κBIα (GG) genotype in contributing to hepatocarcinogenesis. Smoking and alcohol drinking are also risk factors for HCC.