Aim: To assess the up-to-date evidence of acupuncture for the management of cancer-related and cancer treatment-related outcomes among people with advanced cancer. Design: Systematic review with meta-analyses involving multidimensional outcomes. Methods: The protocol of this systematic review has been registered in PROSPERO with the registration number CRD42020212982. Six databases (including Pubmed, EMBASE, Cochrane Library, SinoMed, ClinicalTrials.gov and Chinese Clinical Trial Registry) will be searched from inception through November 2020 to identify relevant interventional trials examining acupuncture management on multidimensional outcomes in patients with advanced cancer. Main outcomes will include cancer and treatment-related symptoms, quality of life, sleep quality and adverse events. DerSimonian & Laird random-effects meta-analysis will be applied to calculate pooled relative risks for binary data and pooled weighted mean differences (WMDs) or standardized mean differences (SMDs) for continuous data. Trial quality ratings and risk of bias will be evaluated using the Cochrane Risk of Bias Tool and the Grading of Recommendations Assessment, Development and Evaluation approach. Discussion: The efficacy of acupuncture on advanced cancer care and outcomes has not yet been determined. Palliative care for patients with advanced cancer may involve multiple challenges that include physical and mental health care. This systematic review will offer updated and comprehensive evidence of acupuncture on specific outcomes induced by advanced cancer and cancer-related treatment, which can give high level clinical recommendations to improve patient care and clinical outcomes.