Objective: Acceptance and Commitment Therapy (ACT) tries to increase the psychological acceptance of individuals during mental experiences (thoughts, emotions, etc.) and to decrease their ineffective control of behaviors. This study aimed to determine the impact of ACT on the psychological flexibility of students with thalassemia in Zahedan City, Iran. 
Methods: The present study was a quasi-experimental interventional study with experimental and control/ waiting groups. The subjects were evaluated in the pre-test, post-test, and two-month follow-up stages. The statistical population included all students with thalassemia studying in senior elementary and junior high schools in Zahedan. A total of 60 volunteers were selected and randomly assigned into two groups (control and experimental), each one including 30 subjects. The research tool was the Psychological Flexibility Test. ACT was conducted during 8 sessions (Two 120-minute sessions per week during one month), and a follow-up test was taken two months after the end of the intervention. The study data were analyzed through repeated measures analysis of variance. 
Results: The results indicated a significant effect of ACT on increasing the cognitive flexibility in patients with thalassemia and supported the stability of this psychotherapy at the follow-up stage (F=63.823, P=0.001).
Conclusion: ACT can be used to increase cognitive flexibility and to treat psychological disorders. Comparing cognitive flexibility scores of the samples in the pre-test, post-test, and follow up stages suggest that ACT is an effective method for improving cognitive flexibility in students with thalassemia major.