【Objective】 To analyze the epidemiologic and clinical features of 53 fatal cases of hand, foot and mouth disease(HFMD) in Shandong province in 2009-2010,so as to provide scientific basis for reducing mortality and optimizing treatments for severe cases. 【Methods】 Epidemiological investigations and laboratory tests were carried out on these fatal cases,and descriptive epidemiology was used to analyze acquired information. 【Results】 The average age of fatal cases was 1 year 6 months,and cases under 2-year-old accounted for 83.0%.The number of deaths from rural areas was larger than that of urban areas.The death ratio between male and female was 3.4∶1.Death cases were dominated by EV71 infection(13/15),with the average course (82.4±4.7) h.96.9% cases had fever from onset,then rash occurred after 1.06 days.Most cases also had other clinical manifestations, such as convulsion,irritability,lethargy,myoclonic twitching,short of breath,dyspnea,respiratory rhythm changes,pink foaming from mouth,lung moist rale,cardiac rhythm changes or vomiting.Primary causes of death was ranked as neurogenic pulmonary edema (96.9%),encephalitis (65.6%) or respiratory and circulatory failure (46.9%). 【Conclusions】 Death cases under 2-year-old had shorter course and higher case fatality rate. In order to reduce deaths of HFMD,it is of vital importance to strengthen monitoring of severe patients, to enhance the ability of early recognition and sensitivity of severe clinical manifestations,to take treatment earlier and to slow down the progression of the disease.