IntroductionHepatitis B virus (HBV) infection causes serious liver diseases and is a healthy problem worldwide. Although vaccines are administered to infants after birth, there is no effective medicine for HBV infection. The interferon-stimulated genes (ISGs) are important factors in the host that can aid in restraining the virus, and theC19orf66gene has a wide-antiviral spectrum.MethodsIn this study, three SNPs in theC19orf66gene were sequenced and genotyped, and their potential function were predicted and further verified by dual-luciferase reporter assay.ResultsAlthough no significant difference of genotype and allele frequency was observed between HBV patients and the controls, the genotype and allele frequency showed significant difference between HBV patients with HBsAg-positive and HBV patients with HBsAg-negative or controls. Genotype AA (P= 0.009) and AT (P= 0.019) of rs77076061 showed higher and lower frequency in HBV patients with HBsAg-positive than in patients with HBsAg-negative, respectively. Genotype AG of rs1979262 played a risk role in HBV patients with HBsAg-positive (13.22%) than in patients with HBsAg-negative (7.53%,P= 0.036) or controls (8.48%,P= 0.033). The frequency of allele A of rs1979262 was higher in patients with HBsAg-positive (6.61%) than in patients with HBsAg-negative (3.77%,P= 0.042), while it was the opposite for the allele G. Moreover, the associations between genotypes of SNPs in theC19orf66gene and the ALT, AST, and DBIL level were also identified. The functional assay suggested that the SNPs might influence theC19orf66expression by changing the connection of transcriptional factors.ConclusionIn summary, the association between genetic polymorphisms in theC19orf66gene and HBV infection/biochemical indices of patients was firstly identified in Yunnan Province.