Objective:To investigate the risk factors of Hand-foot-mouth disease (HFMD) in Changzhou. Methods:A case-control study involving interviews with 108 newly diagnosed HFMD cases and equal number of controls matching for age and sex were carried in Changzhou. Statistical analyses of single-factor and multivariate conditional logistic regression were performed to investigate the risk factors of HFMD. Results:By using single-factor analysis,5 exposure factors were identified as aetiological factors for HFMD. Multivariate conditional logistic regression analysis showed 2 main risk factors and 1 protective factor for HFMD. There were:living in rural areas with odds ratio (OR) 2.191 (95%CI:1.174~4.088),drinking unboiled water habit with OR 2.441 (95%CI:1.050~5.675),washing their hands before and after meals with OR 0.505 (95%CI:0.259~0.983). Conclusion:Good sanitation,family’s and individuals’ good health habit are important factors to prevent HFMD. This study provides an important theoretical support for future health propaganda and education of HFMD.