The present paper aims to investigate the prevalence trends, early clinical characteristics and treatment experience of hand, foot and mouth disease complicated with brain injury. The outpatients clinically diagnosed as hand, foot and mouth disease and inpatients with severe hand foot and mouth disease diagnosed by comprehensive analysis in our chilidren’s hospital from August 1, 2008 to July 31, 2009 were chosen. The clinical manifestations, laboratory examination, treatment and outcome data from 43 cases of patients with hand, foot and mouth disease complicated with brain injury were retrospective analyzed. The results showed that hand, foot and mouth disease occurred throughout the year. The incidence of hand, foot and mouth disease complicated with brain injury was 1.57%, which mainly occurred from May to October. The average age of patients was 2.89 years old, with the youngest of 5 months old and the oldest of 13 years old. In clinical classification, brain stem encephalitis accounted for 48.8%, encephalitis accounted for 32.6%, meningoencephalitis accounted for 18.6%. Administration of mannitol, methyl-prednisolone, intravenous gamma globulin, and mechanical ventilation for those precursors of pulmonary edema as early as possible was the main treatment measure. Among the patients, 98% had a good prognosis. The hospital average length of stay was 11.1 d. The survey confirmed that the incidence of hand, foot and mouth disease complicated with brain injury was 1.57%, occurring mainly from May to October, and brain stem encephalitis is common. Early diagnosis, effectively reducing intracranial pressure, rational use of high-dose intravenous gamma globulin and short-term high-dose hormone are effective measures in preventing disease progression.