Abstract: OBJECTIVE To study the expression and significance of microRNA 27 a（miR-27 a） and microRNA 206（miR-206） in children with hand foot mouth disease（HFMD） infected by enterovirus 71（EV71）. METHODS Total of 66 cases of EV71 infected children with HFMD in our hospital from Nov 2019 to Nov 2020 were recruited and divided into the EV71 infection group; 30 uninfected healthy children in the same period were in the control group. Venous blood was collected from all children to detect the expression levels of serum mir-27 a and miR-206, and the relationship between the expression levels of serum mir-27 a and miR-206 and EV71 infected HFMD was analyzed. RESULTS The expression of miR-27 a and miR-206 in the EV71 infection group was significantly lower than that in the control group; the expression of miR-27 a and miR-206 in critically ill children was significantly lower than those in severe and common children; the expression of miR-27 a and miR-206 in severe children was significantly lower than that in common children（P＜0.05）. Multivariate Logistic regression analysis showed that low expression of serum miR-27 a and miR-206, WBC and CRP were risk factors for HFMD caused by EV71（P＜0.05）. The area under the curves（AUCs） of miR-27 a and miR-206 for the prediction of HFMD were 0.703 and 0.768, respectively. CONCLUSION The expression levels of miR-27 a and miR-206 in serum of children with HFMD infected by EV71 significantly decreased. Low levels of miR-27 a and miR-206 were risk factors for the prediction of EV71 infected children with HFMD.