Objective: To explore the influence of outpatient health education on cognitive behavior and mental health of parents of children with hand-foot-mouth disease (HFMD). Methods: A total of 100 HFMD children and their parents were selected as the study objects. The software of computer random grouping was used to divide them into a control group and an observation group. The control group was given the traditional outpatient health education. The observation group paid more attention to and gave full play to the role of parents in the home isolation of HFMD children on the basis of the traditional health education. A series of intervention measures were carried out to improve the quality of outpatient health education for parents of HFMD children, all of which were followed up for 4 weeks. Compared with the remission of symptoms and signs of HFMD in the 2 groups, the cognitive status and compliance behavior of parents of the 2 groups before and after the intervention were mainly evaluated by the last follow-up questionnaire survey. The mental health status of parents of the two groups was evaluated by Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS). Results: The recovery of body temperature, disappearance of herpes and improvement of appetite of HFMD children in the observation group were significantly shorter than those in the control group (P<0.05). After 4 weeks of parent intervention, the cognitive scores of “HFMD transmission pathway” “disinfection and isolation” “herpes care”, “disease observation” and “complication prevention” in the 2 groups were significantly improved (P<0.05), and the above scores in the observation group were higher than those in the control group (P<0.05). The compliance rates of “disinfection and isolation measures” “washing hands before and after meals” “tableware and bedding hygiene” and “opening windows and ventilation at home” in the observation group were significantly higher than those in the control group (P<0.05). After 4 weeks of intervention, the scores of SAS and SDS in the parents of the two groups were significantly lower than those before intervention (P<0.05). After the intervention, the scores of SAS and SDS in the parents of the observation group were significantly lower than those in the control group (P<0.05). Conclusion: To pay attention to the main role of parents in home-based isolation of children with HFMD, and to take a series of measures to improve the quality of health education of parents’ outpatient service are helpful to alleviate children’s symptoms and signs, improve children’s parents’ disease cognition level, the compliance rate of home-based isolation behavior and improve mental health.