Background: Thalassemia is an inherited blood disorder affecting hemoglobin synthesis that can actually affect the quality of life of children due to the disease and the provided treatment. Aim of the study was to evaluate the effect of educational program based on the precede-proceed planning model on quality of life of children with thalassemia. Design: A quasi-experimental design was used. Setting: This study was conducted at Pediatric Hematology Unit and Pediatric Hematology out-Patient Clinic at Benha Specialized Pediatric Hospital affiliated to Egyptian Ministry of Health and Population and Secretory of Specialized Medical Centers at Benha City. Subjects: A purposive sample of 125 children. Tools of data collection: Two tools were used; Tool I: A structured interviewing questionnaire based on precede-proceed planning model involving five parts; Part (1) Characteristics of the studied children, Part (2) Medical history of the studied children, Part (3) Predisposing factors assessment questionnaire, Part (4) Reinforcement factors assessment questionnaire and Part (5) Enabling factors assessment questionnaire, Tool II: Pediatric Quality of Life Inventory Generic core scale. Results: Less than one quarter and less than three quarters of studied children had high quality of life at pre-and post-intervention phases respectively. While, less than one quarter and 12.8% of them had low quality of life at pre-and post-intervention phases respectively. Conclusion: Children with thalassemia had higher quality of life scores after implementation of the program based on the precede–proceed planning model. Recommendations: Integrating of the precede-proceed planning model in designing intervention programs in pediatric hematology units.