To explore the potential effects of Tai chi on the fatigue-sleep disturbance-depression symptom cluster (FSDSC) among breast cancer (BC) patients.This study was conducted as a preliminary randomized controlled trial among 72 BC patients (36 Tai chi and 36 control participants). All the participants were provided with routine care, while participants in the Tai chi group received an additional 8-week Tai chi intervention. Participants' fatigue, sleep disturbance and depression were assessed by the Brief Fatigue Inventory, the Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale-Depression. Participants' quality of life (QoL) was assessed by the Functional Assessment of Cancer Therapy-Breast. Both covariates-unadjusted and adjusted GEE models were run to assess the effects of Tai chi intervention on the FSDSC and QoL and the relevant impacts of the covariates.Sixty-nine participants completed this study. In the unadjusted GEE model, compared with the control group and baseline, participants in the Tai chi group showed significant reductions in fatigue (p < 0.001), sleep disturbance (p < 0.001) and depression (p = 0.006), as well as a significant improvement in QoL (p = 0.032) at immediately post-intervention and four-week follow-up. The positive regression coefficients of the adjusted GEE model showed fatigue, sleep disturbance and depression can have impacts on each other (all at p < 0.05).Tai chi as an adjuvant intervention to routine care could relieve the symptom cluster of fatigue, sleep disturbance and depression and improve QoL among BC patients.Copyright © 2022 Elsevier Ltd. All rights reserved.