Objective To explore the clinical features and outcome of patients with hand, food and mouth disease (HFMD) with early symptoms of nervous system. Methods The clinical manifestations, laboratory data, therapeutic outcomes and etiology data of 85 hospitalized cases were analyzed, including 62 cases(72.94%) with febrile convulsion (FC) and 23 cases (27.06%) with severe symptoms in early stage (easily fright, limb shaking and somnolence). Results (1) In the FC group, there mainly were the seizures on the first day of fever (1-3 time, lasting 1~10 minutes) , the consciousness were back to normal after convulsion stop, no positive pathological nerve signs, and some patients had the past medical history and family history of convulsion; In the cases with severe symptoms in early stage, easily fright, limb shaking and somnolence appeared on the 3rd~4th day after onset, and disappeared after treatment for 1-3 days. (2) There was no statistically significant difference in duration of fever and rash between two groups, all P>0.05. (3) Most of the patients had elevated blood leukocytes, C-reaction protein, sugar and hyponatremia, some have elevated myocardial enzymes and EKG abnormalities, mainly in the FC group. (4) Pathogen detection: 45 cases (52.94%)- EV71 RNA (+), 19 cases (22.35%)-CoxA16 RNA (+), 12 cases (14.12%)-general intestinal virus nucleic acid (+), 9 cases (10.59%) nucleic acid (-), and no cross positive results. (5)The average hospitalization was 5.86±1.89 day, and sequela was not found in follow-up. Conclusions It is helpful for guiding the treatment and judging the prognosis that the conditions and causes of illness are early identified in patients with HFMD with symptoms of nervous system.