Objective To investigate the typical high risk factors of severe hand,foot and mouth disease(HFMD),especially on critical danger cases through comparison between ordinary type HFMD cases and severe & critical danger cases. Methods Retrospective study was conducted on 128 admitted severe(n=104) & critical danger (n=24,including 9 deaths)HFMD cases from Jan.2008 to Dec.2012,and 128 cases were matched with 143 laboratory confirmed general HFMD,and clinical features and high risk factors were compared between 2 groups above,then,logistic regression was applied to investigate typical clinical features & high risk factors of critical danger HFMD cases. Results 1)Indicators of onset age,whether or not diagnosed at first medical visit,heating time and thermal peak,rash nature,presence of central nervous symptoms(CNS),chest radiographic and cardiovascular manifestations,laboratory defective indexes and proportion of EV71 infection were different between general cases and severe & critical danger cases(P<0.05);2)Atypical rash ratio,neurological symptoms,cardiovascular and chest X-ray manifestations,proportion of EV71 infection and laboratory defective indexes of critical danger cases were more serious or higher than those of severe cases(P<0.05).3)Atypical rashes,neurological symptoms,chest radiography exudative manifestations,elevation of FPG and BP,EV71 infection were severe independent risk factors of critical danger HFMD cases revealed by Logistic regression model (P<0.05). Conclusion Attention should be paid to children with less than 3 years old,atypical rashes and abnormalities of chest X-ray,BP,FPG,etc,those indexes presenting abnormally are deteriorating tips for HFMD cases.