BACKGROUND: Hand, foot and mouth disease (HFMD) is a common illness in China that mainly affects infants and children. The objective of this study is to assess the economic cost and health-related quality of life associated with HFMD in China. METHOD: A telephone survey of caregivers were conducted in 31 provinces across China. Caregivers of laboratory-confirmed HFMD patients who were registered in the national HFMD enhanced surveillance database during 2012-2013 were invited to participate in the survey. Total costs included direct medical costs (outpatient care, inpatient care and self-medication), direct non-medical costs (transportation, nutrition, accommodation and nursery), and indirect costs for lost income associated with caregiving. Health utility weights elicited using EuroQol EQ-5D-3L and EQ-Visual Analogue Scale (VAS) were used to calculate associated loss in quality adjusted life years (QALYs). RESULTS: The subjects comprised 1136 mild outpatients, 1124 mild inpatients, 1170 severe cases and 61 fatal cases. The mean total costs for mild outpatients, mild inpatients, severe cases and fatal cases were $201 (95%CI $187, $215), $1072 (95%CI $999, $1144), $3051 (95%CI $2905, $3197) and $2819 (95%CI $2068, $3571) respectively. The mean QALY losses per HFMD episode for mild outpatients, mild inpatients and severe cases were 3.6 (95%CI 3.4, 3,9), 6.9 (95%CI 6.4, 7.4) and 13.7 (95%CI 12.9, 14.5) per 1000 persons. Cases who were diagnosed with EV-A71 infection and had longer duration of illness were associated with higher total cost and QALY loss. CONCLUSION: HFMD poses a high economic and health burden in China. Our results provide economic and health utility data for cost-effectiveness analysis for HFMD vaccination in China.