Background: Thalassemia is a chronic disease with serious clinical and psychological challenges. The incidence of thalassemia in a family member may cause a psychological crisis in all family members and in this case coping strategies are required. This clinical trial study aimed to determine the impact of training coping strategies on their use by major thalassemic adolescents referred to Dastgheib Hospital in Shiraz.Methods:  In this randomized clinical trial, 87 adolescents with major thalassemia who were randomly assigned to two groups of experiment and control were enrolled. Then the experiment group attended six sessions of coping strategies training program in isolation, each lasting for one and half hour. In order to examine the coping strategies, Jalowice’s coping strategy questionnaire was used in three periods including pre-intervention period and one month and two months after the intervention. The collected data were analyzed using independent t-test and Chi-square.Results: Mean scores of problem-focused coping strategies in the experiment group increased in one month and two months after the intervention from 45±12.7 to 54.8±7.3 and 55.7±7.2, respectively. Also, the difference in mean scores of problem-focused coping strategies was significant in the two groups (P<0.001).  Furthermore, the difference in mean scores of emotion-focused coping strategies was significantly different between the two groups in two months after the intervention (P=0.007).Conclusion: Based on the obtained results, teaching coping strategies has improved the use of problem-focused coping strategies and also effective coping with stress and disease problems in patients with thalassemia major. Therefore, it is recommended that authorities should consider this as a part of treatment program.Trial Registration Number: IRCT2013112215484N1