Abstract: Objective To explore the distribution of cytokines IFN-gamma gene (-1615C/T and +5171A/G)single nucleotide polymorphisms in Guangxi people，and the impact of hepatitis B virus (HBV)infection and primary hepatocellular carcinoma(HCC)occurrence. Methods A case-control study based on hospital was carried out and all the objects were frequency matched by 375 HCC patients - 377 HBV carriers-406 healthy control.TaqMan MGB Real-Time fluorescence quantitative PCR technology was applied to detect the SNPs of the two loci.The distribution of the genotype and the interaction of gene-environment in the three groups were analyzed by Logistic regression model.The linkage disequilibrium and haplotype of IFN-gamma gene were analyzed. Results There was no significant statistically difference in the polymorphisms of -1615C/T and +5171A/G loci among the three groups (P＞0.05).There were gene-environment interactions in smoking，alcohol consumption，liver cancer related family history with IFN-gamma gene according to logistic regression analysis.Alcohol consumption combined -1615 locus mutant gene G increased HBV infection risk(OR=1.72，95%CI:1.11~3.26).The two loci mutant genes combined with liver cancer related family history also enhanced HCC risk (OR:29.24，52.03，95%CI:6.91~123.6，7.02~385.4，respectively).-1615C/T and +5171A/G sites on IFN-gamma had linkage disequilibrium(D′=0.976，P=2.22^-16)，but the haplotypes between HCC groups and the total controls (HBV carriers and healthy control)had no significant statistically difference. Conclusion The mutant genes of -1615C/T and +5171A/G loci might not influence the occurrence of HCC and HBV infection directly in the population of Guangxi，however they enhanced the risk interacted with the environment risk factors.