The results revealed a relationship between the serum concentrations of HMGB1, IL-6, and TNF-α and EV71-induced HFMD, and indicate that HMGB1 is involved in the pathogenesis of EV71-induced HFMD, suggesting that the gene transcription regulation by HMGB1 may play an impotent role during the process of HFMD. This evidence concerns the gene TNF and hand, foot and mouth disease.