In this study, we reported that the frequencies of circulating IL-22+IL-17A−CD4+T (cTh22) cells, circulating IL-17A+CD4+T (cTh17) cells and IL-22+IL-17A+CD4+T cells (IL-22+cTh17) in CD4+T cells from peripheral blood mononuclear cells (PBMCs) during the acute stage of children with EV71-associated HFMD were significantly increased compared to healthy controls (HC); however, the percentages of cTh22, IL-22+cTh17 and cTh17 cells in the mild cases of HFMD were notably decreased compared to the severe cases. This evidence concerns the gene IL22 and hand, foot and mouth disease.