Background: Self- determination theory (SDT) play an integral role in the management of many children with thalassemia. Purpose: The purpose of the study was to assess the effect of the self- determination theory based intervention on quality of life among school age children with thalassemia. Research Design: A quasi experimental design was used. Setting: It was conducted the pediatric thalassemia unit in Menoufia University Hospital. Sample: Purposive sample of 70 children with thalassemia at the previously mentioned setting. Instruments: Three data collection instruments were used: structured interviewing questionnaire, Basic Psychological Needs Satisfaction and Frustration Scale and Standardized QOL checklist. Results: the result of this study showed that there were very highly statistical significant differences between children's knowledge on posttest compared to pretest (3.6±1.1 Vs 1.7±0.6 respectively). Also, children who received self- determination theory based intervention had improved their autonomy, relatedness, competency and quality of life dimensions. Conclusion: It was concluded that implementation of self- determination theory improved knowledge and quality of life dimensions for children with thalassemia on post and follow-up tests than pretest. Recommendation: self- determination theory based intervention about thalassemia should be developed and provided for children in pediatric thalassemia units.