Background: Combination prevention is currently considered the best approach to combat HIV epidemic. It is based upon the combination of structural, behavioral, and biomedical interventions. Such interventions are frequently implemented in a health-promoting manner due to their aims, the approach that was adopted, and their complexity. The impact evaluation of these interventions often relies on methods inherited from the biomedical field. However, these methods have limitations and should be adapted to be relevant for these complex interventions. This systematic review aims to map the evidence-based methods used to quantify the impact of these interventions and analyze how these methods are implemented. Methods: Three databases (Web of Science, Scopus, PubMed) will be used to identify impact evaluation studies of health promotion interventions that aimed at reducing the incidence or prevalence of HIV infection. Only studies based on quantitative design assessing intervention impact on HIV prevalence or incidence will be included. Two reviewers will independently screen studies based on titles and abstracts and then on the full text. The information about study characteristics will be extracted to understand the context in which the interventions are implemented. The information specific to quantitative methods of impact evaluation will be extracted using items from the Mixed Methods Appraisal Tool (MMAT), the guidelines for reporting Statistical Analyses and Methods in the Published Literature (SAMPL), and the guidelines for Strengthening The Reporting of Empirical Simulation Studies (STRESS). This review will be conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. Discussion: The impact evaluation of HIV prevention interventions is a matter of substantial importance given the growing need for evidence of the effectiveness of these interventions, whereas they are increasingly complex. These evaluations allow to identify the most effective strategies to be implemented to fight the epidemic. It is therefore relevant to map the methods to better implement them and adapt them according to the type of intervention to be evaluated.