Background Cancer-related fatigue (CRF) is an extremely common and long-term condition that afects the physical and mental health of oncology patients. While the treatment for CRF with western medicine and non-pharmacological therapy remains uncertain and challenging, traditional Chinese medicine (TCM) has become a trending option for the patients. Based on the fndings from randomized controlled trials (RCTs), this study aims to identify and evaluate the evidence about the efcacy and safety of TCM for CRF. Methods A systematic literature search was conducted according to the PRISMA literature research guidelines. Seven electronic databases including PubMed, the Cochrane Library, Embase, Web of Science, Scopus, China National Knowledge Infrastructure (CNKI) and Wanfang database were searched to identify RCTs which investigated TCM in the treatment of CRF published since inception to December 2022. RCTs comparing TCM with no treatment, placebo, or pharmacological interventions were considered eligible for this review. The Consolidated Standards of Reporting Trials Statement extensions for Chinese herbal medicine Formulas (CONSORT-CHM) and the Cochrane Collaboration’s Risk of Bias tool were used in this review to evaluate the quality and the risk of bias of all included trials. Results A total of 82 RCTs were included in this review, regardless of whether they were published in English or Chinese. After data extraction and results evaluation, 78 trials demonstrated overall efcacy in using TCM for CRF patients compared with the control group, in which 33 trials showed that the efcacy rate was statistically signifcant (p<0.05 or p<0.01). TCM was also shown to be benefcial in improving the scores of relevant scales (e.g., PFS, QoL, TCM syndrome score, other fatigue scales etc.) or physical tests indicators (e.g., cytokines, blood test etc.). The most common herbs found in Chinese medicine were Astragali Radix, Ginseng Radix and Codonopsis Radix. Some TCM products, such as Kangai Injection, Buzhong Yiqi Decoction and Shenqi Fuzheng Injection could provide a reference for medication in this review. A range of non-serious, reversible adverse efects associated with the use of TCM was also reported. However, the result of evaluation showed that none of the trials fully met all the CONSORT-CHM criteria, the quality of included trials was generally poor and the risk of bias was mostly uncertain. Conclusion There is some evidence supporting the efcacy and safety of TCM in managing CRF in this systematic review. However, no clear conclusion can be made due to the inadequate reporting of efcacy and adverse reactions. In view of some concerns about the existing evidence after the evaluation, it is essential to standardizethe comprehensive identifcation and efcacy measurement standards, improve the quality of RCTs and conduct more multicomponent therapies to provide an updated reference for CRF patients medication in the future. The protocol of this systematic review has been registered on PROSPERO (CRD42023413625). [https://www.crd.york. ac.uk/prospero/display_record.php?ID=CRD42023413625].