Objective: Fatigue is the most common symptom negatively affecting cancer patients’ quality of life.The aim of this study was to evaluate the preliminary efficacy and safety of 10.6 μm infrared laser moxibustion for cancer-related fatigue (CRF).Methods: We conducted a randomized placebo-controlled trial among 78 patients with cancer who were diagnosed with CRF.The laser group received 10.6 μm infrared laser moxibustion on ST36 (bilateral),CV4,and CV6acupoints.Each participant received a20-minute treatment session3 times per week for 4 weeks.The sham group received the same treatment duration on the same acupoints,but without infrared laser output.The outcome was change in fatigue as measured by the Brief Fatigue Inventory-Chinese (BFI-C) between groups at Week 4 with additional evaluation at Week 8 for durability of treatment effects.A mixed effects model was used to evaluate the difference in treatment effect over time.Results: Among those randomized,61 (78%) patients completed the entire study.The individuals in laser group had significantly less fatigue than those in sham group (3.01 vs.4.40,p=0.002) at the end of intervention.The improvement in fatigue persisted to Week 8,favoring the laser moxibustion group (3.03 vs.4.26,p=0.006).Laser moxibustion was safe,with three cases of mild local erythema that resolved without medical intervention.Conclusion: Infrared laser moxibustion was safe and efficacious in improving CRF in the Chinese population.Larger studies in more racial/ethnically diverse populations are needed to confirm the benefit of this technique for fatigue in cancer patients.