Objective To study the association between the single nucleotide polymorphisms (SNP) of interleukin (IL)-19 and susceptibility to hepatitis B virus (HBV) infection in children. Methods A case-control study was performed, and 136 children with positive HBsAg (case group) and 297 healthy children with negative HBsAg (control group) were enrolled. PCR and DNA sequencing were used for genotyping. Results There were significant differences in the frequencies of genotypes of IL-19 rs1798 between the case and control groups. The case group also had a significantly higher proportion of children with CG genotype than the control group (P < 0.05). There were significant differences in the frequencies of genotypes and alleles of IL-19 rs2243191 between the HBV infection and non-infection groups among children who born to HBV-positive mothers. The infection group had significantly higher proportions of children with TC and CC genotypes and C allele than the non-infection group (P < 0.05). Conclusions The SNP of IL-19 rs1798 may be associated with susceptibility to hepatitis B in children, and the SNP of IL-19 rs2243191 may be associated with susceptibility to breakthrough HBV infection in children at a high risk of HBV infection.