To study the relationship between the interleukin (IL)6 -572G/C polymorphism and risk of hepatocellular carcinoma (HCC) in men.A hospital-based case-control study was conducted with 500 male HCC patients without tumor history in other organs and 590 healthy male controls without history of tumors or chronic diseases. All HCC cases were diagnosed by histopathology. The controls were recruited from the Department of Orthopedic Trauma and Ophthalmology at the same hospital. The IL-6 promoter -572G/C polymorphism and its genotype variants were detected by real-time fluorescence quantitative PCR. The Chi-squared test and unconditional logistic regression analyses were applied to determine the risk of HCC among men carrying the different genotype variants.The frequencies of alleles and distribution of genotypes in the -572G/C loci were not significantly different between the HCC cases and controls (P more than 0.05). The Chi-squared test indicated that the polymorphisms of the loci were not associated with HCC in our male population. However, after adjusting by multivariate logistic regression, the odds ratio (OR) of HCC for the G allele (CG + GG genotypes) carriers was 1.31 (95% confidence interval (CI): 1.00 - 1.71) compared with the CC genotype. Among the male HBV carriers, the CG genotype increased HCC risk significantly (OR = 1.60, 95% CI: 1.14 - 2.24) compared with the CC genotype. A trend test indicated that HCC risk was significantly increased with the numbers of G alleles (P trend less than 0.05). Breslow-Day tests of homogeneity of the ORs indicated an interaction between hepatitis B virus (HBV) infection and polymorphisms of IL-6 (P less than 0.05). The synthetic odds ratio (OReg) of HBV infection and harboring a G allele was 5.95 (95% CI: 3.99-8.87), which represented a super multiplication interaction.Polymorphism of the IL-6 promoter -572 loci may be associated with HCC occurrence in men. Moreover, there is a super multiplication interaction for HCC risk between HBV infection and harboring the IL-6 G allele.