This study was designed to investigate the effectiveness and safety of massage therapy in cancer-related fatigue (CRF) and to provide a reference for the future management of CRF. Eight databases (PubMed, Embase, Cochrane Library, CINAHL, Sinomed, Chinese Scientific Journal database (VIP), Wanfang, and China National Knowledge Infrastructure (CNKI)) were systematically reviewed from inception to May 2022 for randomized controlled trials. Two reviewers critically and independently assessed the risk of bias using Cochrane Collaboration criteria and extracted correlated data using the designed form. The meta-analysis was performed using RevMan 5.3 to calculate the pooled effect sizes and 95% confidence intervals (CIs). Sensitivity analysis was performed to find the source of the heterogeneity. Publication bias was assessed via funnel plot analysis and the Egger test. A total of 11 qualified studies that included 789 patients (massage therapy group: 389; control group: 400) were included in the meta-analysis. Massage therapy had a marked effect on fatigue in cancer patients [standardized mean difference (SMD) = - 1.69, 95% CI (- 2.46, - 0.93), P < 0.01], especially in breast cancer [SMD = - 1.62, 95% CI (- 2.18, - 1.05), P < 0.01]. Reflexology [SMD = - 2.71, 95% CI (- 4.65, - 0.77), P < 0.01] and Chinese massage [SMD = - 1.14, 95% CI (- 1.95, - 0.33), P < 0.01] can have a more significant effect on fatigue. Massage time is 20 to 40min [SMD = - 2.39, 95% CI (- 4.13, - 0.66), P < 0.01], twice a week [SMD = - 3.46, 95% CI (- 5.47, - 1.45), P < 0.01] for 3-5weeks [SMD = - 2.36, 95% CI (- 3.53, - 1.19), P < 0.01], which is more effective in relieving fatigue in cancer patients. Five studies described the occurrence of adverse events and only two studies had adverse events. Massage therapy can be effective in relieving fatigue in cancer patients. Current evidence suggests that reflexology is the most effective approach to relieve fatigue, particularly in the breast cancer patients. The optimal intervention frequency and cycle for massage therapy is twice a week for 3-5weeks, and the optimal duration is 20-40min.