Objective:To explore risk factors of hand-foot-mouth disease (HFMD) in northern parts of Jiangsu province. Methods:Questionnaire survey was used to investigate the history of children with HFMD in past 3 years retrospectively in 6 counties belong to Yancheng and Huaian. Univariate analysis and multi-logistic regression analysis were used to analyze major risk factors of HFMD. Results: There were 170 HFMD cases in 1 239 study objects with incidence of 50.36/1000 person-years,with 153 outpatient and 17 inpatient cases. Univariate analysis indicated that five exposure factors were related to the occurrence of HFMD;Multivariate analysis showed that there were three risk factors and two protective factors concerned with the prevalence of HFMD,and the factors were depicted as follow:male(OR=1.60,95%CI:1.12-2.27),living in urban(OR=1.71,95%CI:1.15-2.53),children with frequent upper respiratory tract infection,diarrhea and so on (OR=1.96,95%CI:1.20-3.21),breastfeeding only for 3-6 months(OR=0.39,95%CI:0.17-0.84) and washing their hands before and after meals (OR=0.54,95%CI:0.36-0.81). Conclusion: In urban with large density of population,contact transmission was one way of HFMD infection,so reducing children to contact with the patient would be effective to control HFMD spread. In addition,developing good health habits and breastfeeding shoud protect infant and children from HFMD.