Background Hepatitis B infection is one of the most severe hepatic diseases in China. Thus, understanding the genetic pathogenesis of hepatitis B virus (HBV)-infected individuals is important. Although no consistent result is obtained in different populations, HBV treatment effect is reportedly associated with the IL28B gene. Methods To investigate the role of the IL28B gene in HBV-infected individuals in Yunnan, China, we screened genotypes of three single nucleotide polymorphisms (SNPs, rs12979860, rs8099917, and rs12980275) in HBV-infected individuals and general controls by using SnapShot and sequencing. Results Results showed no significant difference was found in genotypes, alleles, and haplotypes frequency between the HBV-infected individuals and controls. After dividing the HBV-infected individuals into patients in acute infection, chronic HBV patients, and patients undergoing convalescence, the genotype GT (P = 0.033) and allele G (P = 0.038) of rs8099917 showed statistically higher frequency in the acutely infectious individuals than in the HBV patients undergoing convalescence. HBV viral load was higher in the acutely infectious patients than in the chronic infection group. Strikingly, we found that leukomonocyte (LYM) level was associated with SNPs in the IL28B gene. In addition, the LYM levels were lower in the HBV-infected individuals with genotype CC of rs12979860 and AA of rs12980275 than in the patients with other genotypes of these two SNPs. Conclusion Our results suggested genetic polymorphisms of the IL28B gene were associated with LYM level of HBV-infected individuals.