This study aimed to investigate the association between the polymorphisms of IL-15 gene and susceptibility to chronic hepatitis B virus (HBV) infection in the Chinese Han population. A total of 234 patients with chronic HBV infection and 150 age-and sex-matched healthy controls in the Chinese population were enrolled in this case-control study. Genotyping of ten single nucleotide polymorphisms (SNPs) in the IL-15 gene was carried out via Sequenom MassARRAY system. The association analysis demonstrated that SNP rs3806798 (A/T) had a significant difference in the distribution between patients and healthy controls (P = 0.033). Moreover, a significantly increased risk of HBV infection was found to be associated with IL-15 rs3806798 A allele among male patients and HBeAg-negative patients, compared with IL-15 rs3806798 T allele (P = 0.003; P = 0.046, respectively). Furthermore, haplotype analysis revealed that haplotype ATAGG (rs3806798, rs12508866, rs1519551, rs6819823 and rs2857261, respectively) in block 1 was significantly associated with HBV infection (P = 0.022). In conclusion, we found an association between IL-15 rs3806798 and the risk of chronic HBV infection in a sample of Chinese Han population.