Background: The number of cases of hand, foot, and mouth disease increased in Egypt in 2022.However, no previous studies done in Egypt regarding this disease. Aim of the study: assess mothers' knowledge, beliefs, and practices regarding Hand, foot, and mouth disease in El-Beheira governorate. Design: A descriptive exploratory research design was adopted to conduct the study. Subjects: A convenient sample of 400 mothers was involved in the study. Setting: The study was conducted at 8 public primary health care facilities in four health directorates in El Beheira Governorate namely: Damanhour, Abo Humus, Itay Elbaroud, and Kom Hamada. Data Collection Tools: four tools were utilized; Tool I: Basic data structured interview schedule, Tool II: Mother's knowledge regarding HFMD scale, Tool III: Mothers' beliefs regarding HFMD scale, Tool IV: Mothers reported preventive practices regarding HFMD scale. Results: About three fifths of the respondents (59.25%) had good knowledge about HFMD. In addition, the highest total mean score was for the dimension of perceived susceptibility and perceived benefits (11.58±3.373and 11.51± 3.486 respectively) and the lowest total mean score was for the dimension of perceived barriers (7.4±3.19).Also, the total mean percent score of mothers' beliefs about HFMD was (65.93±16.350) which denotes that the mothers had more positive beliefs concerning HFMD. Moreover, more than half (54.8%) of the studied mothers had good preventive practices concerning HFMD. Conclusion: It can be concluded that more than half of the respondents had satisfactory knowledge, positive beliefs, and good practices concerning HFMD. Recommendations: Conducting educational programs to enhance mothers' knowledge and practices concerning HFMD