Abstract: Objective To explore the relationship of transforming growth factor beta 1(TGF-β1) gene rs1800469 and interleukin 12B(IL-12B) rs3212227 polymorphisms with the susceptibility to hepatocellular carcinoma(HCC).Methods A hospital-based case-control study was conducted in 608 cases with HCC and 612 controls matched for age,sex,nationality,and residence in Guangxi Zhuang Autonomous Region.Genotypes of TGF-β1 gene rs1800469(-509 C > T) and IL-12B gene rs3212227(3'UTR+1188A > C) were determined by real-time polymerase chain reaction with TaqMan MGB probe.Results The C allele mutation frequencies of IL-12B rs3212227 in the control group and case group were 43.5% and 48.9%,with a significant difference between the two groups(P < 0.05).Compared with wild rs3212227 AA genotype,the IL-12B rs3212227 C allele(adjusted odds ratioOR=1.336,95% confidence intervalCI:1.040-1.717) was a significant determinant factor for HCC.The IL-12B rs3212227 AC and CC genotype increased the risk of HCC(adjusted OR=1.271,95% CI:0.976-1.655; adjusted OR=1.515,95% CI:1.092-2.102,respectively).No significant association was observed between the CT genotype and the TT genotype of TGF-β1 rs1800469 compared with the CC genotype(adjusted OR=1.087,95% CI:0.852-1.386; adjusted OR=1.087,95% CI:0.766-1.542,respectively).The stratified analyses revealed that the AC+CC genotype of IL-12B rs3212227 significantly increased the risk of HCC among the female and the subjects aged less than 55 years(adjusted OR=2.036,95% CI:1.169-3.548; adjusted OR=1.529,95% CI:1.129-2.071,respectively).No interaction was observed between TGF-β1 polymorphisms and the risk factors including age,smoking,alcohol drinking,and hepatitis B virus infection for the development of HCC.Conclusion Our results suggest that IL-12B rs3212227 polymorphisms may have independent effects on the susceptibility to HCC in Guangxi population.