BACKGROUND: The efficacy of various massage doses in palliative cancer care settings is still debated, and no specific protocol is available. AIM: Evaluating response to various massage doses for symptom cluster of pain-fatigue-sleep. DESIGN: A 7-arm randomized-controlled trial with weekly massage for 4 weeks depending on the prescribed dose (15-, 30-, or 60-min; 2× or 3×/week) and a 4-week follow-up. The intensities of pain, fatigue, and sleep disturbance were measured using a 0-10 scale at nine-timepoint; baseline, weekly during the intervention, and the follow-up period. Then, the mean scores of the three symptoms were calculated as the symptom cluster intensity at each timepoint. IRCT.ir IRCT20150302021307N5. SETTING/PARTICIPANTS: Adults with cancer ( RESULTS: The odds of clinical improvement (at least 30% reduction in symptom cluster intensity from baseline) increased with dose-escalation significantly [(OR = 17.37; 95% CI = 3.87-77.90 for 60-min doses); (OR = 11.71; 95% CI = 2.60-52.69, for 30-min doses); (OR = 4.36; 95% CI = 0.94-20.32, for 15-min doses)]. The effect durability was significantly shorter at 15-min doses compared to 30- and 60-min doses. The odds of improvement for doses 3×/week was not significant compared to doses 2×/week (OR = 12.27 vs OR = 8.34); however, the effect durability for doses 3×/week was significantly higher. CONCLUSIONS: The findings indicated that dose-escalation increases the efficacy of massage for the pain-fatigue-sleep symptom cluster. Although the 60-min doses were found to be more effective, the 30-min doses can be considered more practical because they are less costly and time-consuming. Our findings can be helpful to develop massage guidelines in palliative care settings. TRIAL REGISTRATION: Iranian Registry of Clinical Trials, IRCT20150302021307N5.