Abstract: OBJECTIVE To explore the association of gene polymorphisms of interleukin-10（IL-10） and Toll-like receptor 9（TLR9） with Epstein-Barr virus（EBV） infection in children. METHODS A total of 368 children with EBV infection who were treated in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from May 2018 to Apr 2019 were enrolled in the study, 128 of whom had infectious mononucleosis（IM） caused by EBV infection and were assigned as the IM group, 240 had simple EBV infection and were assigned as the simple EBV group. Meanwhile, 100 healthy children who did not have EBV infection were chosen as the control group. The polymorphisms of IL-10 gene（ rs1800896 locus, rs1800871 locus, rs1800872 locus） and TLR9 gene（rs187084 locus, rs352139 locus, rs1352140 locus） in peripheral blood of all the children were detected by polymerase chain amplification reaction. The frequencies of genotypes and alleles of single nucleotide polymorphism（SNP） were observed and compared among the three groups of children. RESULTS All of the 6 loci of IL-10 and TLR9 gene were in line with Hardy-Weinberg balance（P＞0.05）. There were no significant differences in the genotypes and alleles at IL-10-rs1800896, IL-10-rs1800871, IL-10-rs1800872 loci and TLR9-rs187084, TLR9-rs352139 and TLR9-rs1352140 loci among the IM group, the simple EBV group and the control group. The mutation rates of AG genotype at IL-10-rs1800896 locus of the IM group, the simple EBV group and the control group were respectively 9.38%, 8.33% and 14.00%, no GG genotype was found, and the frequencies of G allele were 4.69%, 4.17% and 7.00%, respectively. CONCLUSION There is no association between the polymorphisms at IL-10-rs1800896, IL-10-rs1800871, IL-10-rs1800872, TLR9-rs187084, TLR9-rs352139 and TLR9-rs1352140 loci and the susceptibility to EBV infection.