Abstract: Objective　To summarize the clinical features and diagnostic and management experience of moderate to severe hand, foot and mouth disease (HFMD) cases occurred from May 1 to June 2, 2008 in one city and provide reference for the diagnosis and management of HFMD in other cities. Methods　A total of 1001 HFMD cases were reported from May 1 to June 2, 2008, including 20 severe cases. The author had summarized the diagnostic procedures for this outbreak and the clinical manifestations and management of severe children cases. Results　Clinical manifestations of severe HFMD cases included: the majority of sick children were under the age of three (average 23.6 19.2 months), maximum temperature 39 ℃ (average 39.52 ℃0.39 ℃); the neurological complication occurred within 1 to 4 days after fever (average 2.35 0.99 d); neurological complication presented as aseptic meningitis, the major symptoms included fatigue (60.0%, 12/20), irritation (55.0%, 11/20), involuntary movement of the extremities (45.0%, 9/20), and lethargy (35.0%, 7/20). No statistical difference was observed on the clinical manifestations between 12 children cases infected with EV71 and the other 6 children cases infected with gastro intestinal virus (non EV71, non CoxA16). The DNA detection rate was 83.3% for throat swabs (15/18), and 94.4% for cerebrospinal fluid samples (17/18). The treatment according to disease phase was effective, the case fatality rate was 0. Conclusion　The HFMD cases in this outbreak were in relatively less serious condition, and aseptic meningitis was the major neurological complication. Hospitalized observation should be given when patients' body temperature exceed 39 ℃ and are in four days of illness. Phase specified treatment is effective.