Purpose/Significance To establish the overall framework of differential diagnosis model of hand-foot-and-mouth disease(HFMD), so as to effectively promote the prevention and control of infectious diseases and promote the construction of smart public health system. Method/Process The diseases that need to be identified with HFMD and their differential diagnosis points are determined by referring to literature data. The degree of specific association between a symptom and the disease is assigned by Meta analysis, and the differential diagnosis model based on similarity algorithm is constructed. Result/Conclusion The early and large-scale monitoring and early warning of HFMD has been realized, and the level of intelligent identification, diagnosis and early warning of HFMD has been further improved.