Introduction: Breast cancer is the most common cancer and the second leading cause of death among women with many physical and psychological complications, decreasing the patient’ s quality of life. Therefore, the aim of this study was to evaluate the efficacy of acceptance and commitment therapy on the psychological flexibility, post-traumatic growth and quality of life in patients with breast cancer. Method: In a randomized clinical trial design with pre-test-post-test-fallow up paradigm, a sample of 30 breast cancer patients referred to the Alborz province hospitals selected (summer 2018) and randomly were divided into experiment and control groups after gaining inclusion criteria. Acceptance and commitment based treatment protocol was performed in 10 sessions for the experimental group and the control receive no intervention. The psychological flexibility (MFPI), post-traumatic growth (PTG) and quality of life (FACT-B) questionnaires completed by patients before and after therapeutic interventions and in the follow-up phase. Results: The results of mixed analysis of variance showed that the experimental group participants had a significantly higher scores of psychological flexibility, post-traumatic growth and quality of life than the control group. Also, the scores of these variables changed significantly over time from pre-test to follow-up. The interaction of the group in time showed that the participants of the experimental group obtained significantly higher scores in all variables than the control group in the post-test and follow-up stages, which indicated a regular interaction. Conclusion: Acceptance and commitment therapy is effective on psychological flexibility, posttraumatic growth and quality of life in the breast cancer patients and can be used to improve the quality of life in these patients.