Based on the previous findings that the inflammatory process is related to the pathogenesis of HFMD, the activity of HMGB1 in HFMD has not yet been explored, and IL-6 and TNF-α are regulated in HFMD, we designed a prospective study to investigate the alteration of serum HMGB1, IL-6, and TNF-α levels before and after treatment of 82 children with EV71-induced HFMD. This evidence concerns the gene TNF and hand, foot and mouth disease.