Background Previous studies have showed that Guolin Qigong (GLQG) benefit cancer patients, but there is no strict randomized controlled trial (RCT) exploring the efficacy of GLQG in cancer patients.Methods We conducted a RCT of GLQG as compared with a control intervention consisting of stretching.GLQG and stretching sessions lasted 60 minutes each and took place twice a week for 24 weeks.And then they were followed up for 24 weeks.The primary outcome was the change of quality of life (QoL, measured by the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B), with higher scores indicating better QoL).Secondary outcomes included anxiety, depression and clinical indicators which reflect the immune function and tumor development.All participants were assessed on four time-points, at the beginning of the study (T1),after 12 weeks of the intervention (T2), immediately after 24 weeks intervention (T3)and at 48-week follow-up visit (T4).Results GLQG group showed significant improvement on QoL,higher level of TNF-α and IFN-γ, and significantly decreased CA-15.3 level compared with control group over time.The differences were the most significant at the 12-week intervention visit.The results in subjects who practiced more than 4 times and 6 hour per week were similar to that of all subjects, however the improvement of anxiety in the GLQG group was more obvious.Four adverse events maybe potentially attribute to the GLQG intervention, but these adverse events were relieved after further action guidance and correction by the certified GLQG master.Conclusion The study demonstrated the importance of physical exercise in breast cancer patients to some extent.GLQG maybe become a preferential mind-body exercise for improving QoL in cancer patients.