OBJECTIVES: To estimate direct and indirect costs associated with hand, foot and mouth disease (HFMD) in China.  METHODS: Data were obtained from a nation-wide telephone survey of family member of patients with HFMD from Dec, 2013 to Jan, 2014. Patients` numbers were from national infection disease surveillance database. Patients were eligible for the survey if they aged from 6 months to 5 years, had lab-confirmed as EV71, CoxA16 or other Enterovirus infection and without any underlying disease. HFMD-related outpatient and inpatient utilization and costs and direct non-medical costs were recorded. Indirect costs resulting from productivity loss due to absenteeism were estimated using the average income in China. All costs were reported in 2012 US dollar using the exchange rate of 6.18 Chinese Yuan to 1 USD.  RESULTS: A total of 3500 patients were included with 34.3% female. The number of mild, severe and death cases were 2259(64.54%), 1170(33.43%) and 71(2.03%). 2352(67.23%) of patients received inpatient treatment. The mean direct medical costs were $966. Inpatient costs were $904, accounting for 93.5% of direct medical costs. The rest were attributed to outpatient and medications purchased from retail pharmacies. Mean direct non-medical costs were $67, including $20 nutrition costs and $47 transportation. Mean costs associated with productivity loss were $170 and $55 (urban and rural respectively).  CONCLUSIONS: HFMD poses substantial economic burden to payers, patients and society. The majority of total costs are attributed to direct medical costs but indirect costs from productivity loss are also substantial.