The incidence and severity of hand, foot and mouth disease have increased in mainland China since 2008. Therapies and vaccines are currently at different stages of development. This study aimed to determine the social factors associated with the outbreaks and severity of the disease in Chinese children. A multicentre, prospective, case-controlled study was conducted in Shanghai, Chongqing, Guangzhou and Shantou to identify the sociodemographic and behavioural risk factors for hand, foot and mouth disease. Children hospitalized for hand, foot and mouth disease were randomly enrolled from April to November 2011. Stool samples were collected to test for the presence of enterovirus 71 (EV71). A total of 443 children between 1.6 and 68 months of age were enrolled; 304 were uncomplicated cases and 139 were severe cases with central nervous system involvement. The overall detection rate of EV71 was 54.2%, and the positivity rate of EV71 was significantly higher in the severe group than in the uncomplicated group (82.0% versus 40.9%, odds ratio (OR): 8.35, P=0.000). The children of migrant workers (OR: 3.014, P=0.000) and children attending kindergarten (OR: 2.133, P=0.002) were significantly associated with a severe outcome of the disease (OR: 1.765, P=0.026). Our findings indicate that kindergarten attendance and migrant worker parents are the major risk factors associated with severe hand, foot and mouth disease in children <5 years of age. Future public health intervention vaccination campaigns should consider the particular difficulties of achieving high compliance with multiple-dose vaccination regimens in the children of migrant workers.