Hand-foot-mouth disease (HFMD) is an acute infectious disease caused by various enteroviruses. Recently, large HFMD outbreaks caused by enterovirus type 71 (EV71) have been frequently reported in China, posing great threats on children’s health. There is no specific antiviral therapy for severe HFMD, and patient management mainly depends on supportive and symptomatic treatment. Intravenous immunoglobulin (IVIG) is a pharmaceutical preparation of human IgG that is pooled from thousands of healthy blood donors, and contained neutralization antibodies against various enteroviruses, including EV71. IVIG therapy should be carefully administrated for severe HFMD considering its role on passive immunization against EV71 and immune regulation.