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.