Interferon-c (IFN-c) is a pleiotropic cytokine that plays an important role in regulating cellular immune responses. Regulation of IFN-c expression is considered to be strictly controlled at the transcriptional level. Two single-nucleotide polymorphisms (SNPs) within the human IFN-c promoter (at positions À183 and À155) are considered to influence the promoter activity by altering the acting transcription factor-1 (AP-1) binding. We sought to assess the association between the SNPs of the IFN-c promoter and the host susceptibility to hepatitis B virus (HBV) infection, as well as its interaction with age and gender. No polymorphism at positionÀ155 was detected in any of the participants, but a significant difference was found in the polymorphism at position -183 between the cases and controls (G/T and T/T vs. GG; Po0.01, odds ratio (OR) 5 4.50 (95% confidence interval (CI) 5 2.23-9.09). A susceptibility analysis revealed a gradually increased trend of the OR value from the young to the old group (OR 5 3.03, 4.17, and 5.56). Similarly, the association of the À183 polymorphism was markedly different in females (OR 5 5.71). Our data suggest that the polymorphism at position -183 of the IFN-c gene promoter may be associated with susceptibility to HBV infection, and age and gender factors are coordinative risk factors.