Abstract: Objective To understand the economic burdens caused by severe handfoot and mouth disease (HFMD) and its influence factors in Qingdao and explore the method and approach to reduce the economic burden. Methods Questionnaire survey and checking hospital fees system were combined about the disease history,economic burdens of HFMD cases reported in Qingdao in 2014. Results A total of 201 severe HFMD cases were surveyed. The total economic burden were 3 736 707 yuan (RMB) with the direct economic cost of 3 347 603 yuan (RMB) and indirect cost of 389 104 yuan (RMB). Multivariate logistic regression analysis indicated that the influence factors for economic burden included pathogen type, number of medical care seeking before hospitalization and medical institution where the diagnosis was made. Conclusion The economic burden caused by HFMD was heavy in Qingdao. It is necessary to increase the medicare coverage, improve the diagnosis and treatment of severe HFMD in basic-level clinics and control the incidence of HFMD to reduce the economic burden caused by HFMD to society.