Abstract: Objective To probe into the influencing factors of children hand-foot-and-mouth disease (HFMD) and provide scientific proofs to the prevention and control. Methods We selected HFMD cases from the nurseries and kindergartens in the precinct through the year of 2015 and chose healthy subjects with age difference less than one year for 1:1 match as control group based on China information system for disease control and prevention. Regression analyze was performed to analyze the influencing factors. Results Single-factor analysis showed that 12 items were associated with HFMD including the premature infants, the household annual per capita income of last year, the education background of children keeper, house area, whether having any knowledge of HFMD prevention, whether the children have contact with the HFMD patients seven days ago, whether the kids tend to suck the fingers, whether the patients go to the hospital due to other diseases seven days prior to the HFMD, whether the classroom is sterilized, whether the toilet is sterilized, the ventilation condition of classroom, the ventilation condition of children nap room (all P<0.05). Conclusions HFMD patients' isolation, good living surroundings and personal decent hygiene are all significant to prevent and control HFMD spreading.