Autoimmune disease systemic lupus erythematosus (SLE) is associated with increased expression of pro-inflammatory cytokines such as interferons (IFNs) and specific interleukins (ILs), which are induced by toll-like receptors (TLRs). The present study aimed to examine the serum levels of cytokines, the activation of TLR-7 and TLR-8 of peripheral blood mononuclear cells (PBMCs) from pediatric SLE patients, and to investigate the response of those PBMCs to viral RNA via the TLR-7 and TLR-8 signaling. Results demonstrated that pediatric SLE patients had increased serum concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10, and IFN-α, and promoted activation of TLR-7 and TLR-8, compared to control subjects. Moreover, the peripheral blood mononuclear cells (PBMCs) from pediatric SLE patients were more sensitive to the stimulation by the transfection with viral RNA from influenza virus, with a promoted activation of TLR-7 and TLR-8 signaling. In conclusion, pro-inflammatory cytokines, such as IL-1β, IL-6, IL-8, IL-10, and IFN-α were promoted in pediatric SLE patients, with an increased activation of TLR-7 and TLR-8 to the stimuli, such as virus infection. It implies the TLR-7 and TLR-8 activation by virus infection might play an important role in the pathogenesis of pediatric SLE.