Background:Thalassemia as a chronic disease could affect different aspects of a patient’s life. On the other hand, when encountering the symptoms of a chronic disease as a stressful factor, the coping strategy of the adolescents and their families could have an important role in the quality of life of these patients. The present study was conducted to determine the relation between different aspects of quality of life with coping styles in the adolescents with thalassemia in comparison to a healthy control group. Materials and Methods: The present study is a case-control research in 2017. Studied samples were 200 adolescents with thalassemia and healthy adolescents. Data gathering tools were demographic characteristics checklist and the coping style and quality of life questionnaire by the World Health Organization. Data were analyzed by SPSS 20 using independent t-test, linear regression and correlation coefficients. Conclusion:Results of Pearson statistical test showed a positive and significant relation between the total mean score of quality of life and its physical, social and mental aspects with emotion-oriented coping style (p