Abstract: OBJECTIVE To explore the association of human herpesvirus 6（HHV 6） infection and interleukin-18（IL-18） gene polymorphism with susceptibility to rheumatoid arthritis（RA）. METHODS A total of 80 RA patients who were treated in Lishui People's Hospital from Dec 2019 to Dec 2021 were recruited as the study subjects and assigned as the RA group, meanwhile, 80 healthy people who received physical examination were chosen as the control group. The positive rate of HHV 6 DNA in peripheral blood mononuclear cells（PBMCs） and plasma was detected by nested polymerase chain reaction（nested-PCR）, the gene polymorphisms at-607C/A locus and-137G/C locus in promoter region of IL-8 gene were detected by PCR quantitative amplification technique. Multivariate logistic regression analysis was performed for the relationship between the HHV infection, IL-8 gene polymorphisms and the susceptibility to RA. RESULTS There was no significant difference in the positive rate of HHV 6 DNA in PBMCs between the two groups, while the positive rate of plasma HHV 6 DNA of the RA group was higher than that of the control group. The positive rate of plasma HHV6 DNA of the patients with serum rheumatoid factor（RF） concentration no less than 60 IU/ml was higher than that of the patients with the serum RF concentration less than 60 IU/ml（P＜0.05）; the positive rate of plasma HHV6 DNA of the patients with high activity of disease was higher than that of the patients with disease modifying, moderate to low activity of disease（P＜0.05）. There were no significant differences in the frequencies of genotypes and alleles at-607C/A locus of IL-18 gene between the two groups, while the frequencies of GC genotype and C allele at-137G/C locus of IL-18 gene were higher in the RA group than in the control group（P＜0.05）. Multivariate logistic regression analysis indicated that the plasma HHV6 DNA-positive patients were 3.089 times the risk at RA as the negative patients（95%CI:1.289-7.405）, the patients carrying with GC+CC genotype at-137G/C locus of IL-8 gene were 2.524 times the risk at RA as the patients carrying with genotype GG（95%CI:1.338-4.764）. CONCLUSION The active infection of HHV6 and gene polymorphisms at-137G/C locus of IL-8 may be associated with the susceptibility to RA.