Background: Children with thalassemia are more exposed to physical, psychological, environmental and social problems and the families have a crucial role in caring for thalassemic children. Aim: To assess family management and its relation to health-related quality of life among thalassemic children. Research design: A descriptive research design was used to fulfill the aim of the study. Sample: A purposive sample included 103 of families with thalassemic children. Data Collection Tools: Tool (I): A structured interviewing questionnaire includes two parts. Part 1: Demographic characteristics: A: Background information of parent. B: Background information of the child. Part 2: Family Management Measure (FaMM). Setting: This study was performed at a hematology clinic in the Minia Regional Blood Bank.Tool (II): Pediatric Quality of Life Inventory Version 4.0™ parent proxy-report (PedsQL™ 4.0). Results: 62.2% of the studied families have a poor level of family management measures toward thalassemic children with Mean of 74.44±12.70 and also 60.2% of the studied families reported that have a poor quality of life for their children with mean of 65.1±10.20. Conclusion: a positive correlation was found between the total family management and the total level quality of life, some sociodemographic characteristic such as residence, education, income and number of family members were associated with family management measures and also with the parents' perception of their children's quality of life among families of thalassemic children. Recommendations: health education programs should be given about family management and its relation to health-related quality of life among thalassemic children. Community health nurses should collaborate with other health team members to implement comprehensive educational sessions about endogamy mirage and its significant relation to thalassemic disease.