Objective To analyze the clinical features of severe hand-foot-mouth disease (HFMD)combined with encephalitis.Methods The cases with HFMD in our hospital from September 2009 to September 2010 were divided into two groups including the ordinary case group(n =235) and the encephalitis group (n =88).Clinical manifestations were analysed between the two groups.Results There were significant differences in number of oral ulcers,degree and duration of fever between two groups (P ＜ 0.05).Eighty percent cases of the ordinary group had multiple or dense herpes or ulcers,which was more than that of the encephalitis group.But there were no significant differences in WBC and its classification in peripheral blood between two groups (P ＞ 0.05).There were obvious differences in CK,CK-MB,AST,GLU of blood between two groups (P ＜ 0.05).The contents of protein,glucose and chloride in cerebrospinal fluid have no differences between two groups (P ＞ 0.05),besides the cell count.The cell count in cerebrospinal fluid of cases with enterovirus infected encephalitis was significantly higher than those with CoxA16 infection(P ＜ 0.05).Conclusion The patients with few rash,less oral herpes,ulcers or high levels of CK,CK-MB,GLU should be closely observed to vigilant merger encephalitis.The cases with severe H-FMD have middle or high fever and duration of fever are more than 4 days.The increased cell count in cerebrospinal fluid may imply encephalitis with enterovirus 71 infection.