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Objective: To synthesize the evidence of the effectiveness of topical treatment compared to the systemic treatment for pain control in Malignant Fungating Wounds (MFWs) in adults. Introduction: Approximately 14.5% of cancer patients present MFWs due to the increased survival rate of oncology treatments, and 85% report pain in the wound. Previous systematic reviews on the subject have explored MFWs-related symptoms (bleeding, foul odor, and exudate) but without results concerning the pain. A recently published scoping review mapped 20 proposals for topical treatment of MFWs-related pain, originated in different studies designs. Currently, there is a need to carry out an effectiveness review in order to facilitate clinical evidence-based decision-making. Inclusion criteria: Quantitative studies on the effects of topical therapies for pain control in MFWs compared to systemic treatments in adult patients in English, Portuguese, and Spanish without any time limits. Studies that do not meet 70% of the methodological quality threshold will be excluded. Methods: A review of effectiveness according to the JBI methodology. The titles and abstracts of identified records will be checked for the inclusion criteria, and the selected papers will be reviewed in their entirety for their relevance to the objective. The selection of the studies will be carried out according to the defined threshold of the assessment of the methodological quality using the JBI Critical Appraisal Checklist instruments, and the data of interest will be extracted by two reviewers. Finally, the data synthesis will be presented in a narrative and/or statistical summary. Systematic review registration number: CRD42022351715