Abstract: OBJECTIVE To investigate the expression of nuclear factor-κB（NF-κB） signaling pathway in children with Kawasaki disease（KD） epstein-Barr virus（EBV） infection and its effect on the release of inflammatory cytokines and coronary artery lesion（CAL）. METHODS A total of 89 children with KD admitted to Pediatrics Department of Fuzhou First People's Hospital from Dec 2017 to Dec 2020 were selected and divided into 30 cases of EBV infection group and 59 cases of non-EBV infection group according to the results of EBV DNA testing. The expression levels of serum inflammatory factors interleukin（IL-6, IL-8, IL-10, IL-1β）, tumor necrosis factor α（TNF-α）, matrix metalloproteinase（MMP-2, MMP-9） and its tissue inhibitor of metalloproteinase-1（TIMP-1）, NF-κB and its profilin（IκBα） were detected by enzyme-linked immunosorbent assay（ELISA）. The levels of NF-κB and IκB mRNA were detected by real-time fluorescent quantitative polymerase chain reaction（PCR）. The incidence of CAL in both groups was calculated. RESULTS The levels of peripheral blood white blood cell count, serum IL-6, IL-8, IL-10, IL-1β, TNF-α, MMP-2, MMP-9, NF-κB and its mRNA in the EBV infection group were significantly higher than those in non-EBV infection group, while levels of TIMP-1, IκBα and its mRNA were significantly lower than those in non-EBV infection group（P＜0.05）. The incidence of CAL in EBV infection group was 43.33%（13/30）, significantly higher than that in non-EBV infection group（P＜0.05）. CONCLUSION The levels of inflammatory cytokines in peripheral blood of children with KD combined with EBV infection were up-regulated, and incidence of CAL was significantly increased. EBV infection may mediate inflammation response by activating NF-κB signaling pathway and cause CAL.