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Purpose: Several lines of clinical research support the efficacy of Cognitive behavioral therapy (CBT) with a large number of population and various disease conditions, however, the true effects of CBT interventions on Quality of Life of breast cancer patients remain unknown. The aim of the study was to evaluate the effect of Cognitive Behavioral Therapy on the Quality of Life of breast cancer patients. Methods: A systematic review of articles published using Web of Science (1950–January 2020); Medline via EBSCO (1992–January 2020); Science direct via ELSEVIER (1996–January 2020); SCOPUS (2004–January 2020); and PubMed (1946–January 2020 excluding Medline from 1992–January 2020) were included. Additional studies were included after checking reference lists of all relevant studies; searching ongoing trials and research registers and manual search. Data extraction was conducted by two independent authors and a third independent author checked the data extraction. The PRISMA statement was adopted. Result: Eleven Randomized controlled trials (RCT) with 1690 breast cancer patients were included in this review. The overall effect size of cognitive behavioral therapy on QoL of breast cancer patients was medium 0.39 (95% CI 0.12–0.66, P < 0.00001, I2 = 83%). Five studies had shown statistically significant improvement in functional and symptoms scales in the treatment group than the control group. Conclusion: CBT is effective in improving the Quality of Life of breast cancer patients. In future research, further randomized controlled trials with adequate randomization, allocation concealment, and appropriate blinding may be needed. [ABSTRACT FROM AUTHOR]