Objective:To analyze the differences in clinical features of severe hand,foot,and mouth disease caused by different en-teroviruses(EV),and to provide scientific evidence for its clinical diagnosis,treatment,and prevention. Methods:A total of 421 children admitted and diagnosed with severe hand,foot,and mouth disease in Children’s Hospital of Chongqing Medical University from April 2016 to April 2017 were selected,and quantitative real-time PCR was used to detect EV. Excluding 13 children with unclear re-sults,408 children were included in the final study. According to EV strains,the children were divided into EV71 group,non-EV71 group,and EV-negative group to compare their clinical features. Results:Among the 408 children,137(33.59%) were positive for EV71,212(51.96%) were positive for non-EV71,and 59(14.46%) were negative for EV. The EV71 group had a significantly longer duration of fever than the non-EV71 group(P=0.000) and the EV-negative group(P=0.017),and had a significantly higher inci-dence of limb tremor(P=0.002) and headache(P=0.003) than the non-EV71 group. The non-EV71 group had a significantly higher incidence of skin rash on the mouth(P=0.003),limbs(P=0.001),and trunk(P=0.006) than the EV71 group,but had a significantly shorter duration of skin rash than the EV71 group(P=0.000) and EV negative group(P=0.015). Conclusion:Patients with severe hand,foot,and mouth disease caused by EV71 have more severe symptoms of fever and neurological involvement than other groups,while those caused by non-EV71 have a wider distribution but a shorter duration of rashes.