BackgroundKey populations who bear a disproportionate burden of HIV, including female sex workers, men who have sex with men, people who use drugs, transgender people, and incarcerated populations, have been understudied, especially in the context of broadly generalized HIV epidemics. Program and investment planning documents often do not take into account the data that do exist. Prior systematic reviews have been comprehensive, but lack sustainability and relevance over time. This review aims to synthesize all available data for key populations and present the data through an accessible, updatable user-friendly graphic interface. The outputs of this systematic review will serve as a resource for decision-makers, providing government stakeholders and donors with the tools to make evidence-based decisions for national planning.MethodsWe will conduct a systematic review of data published or made available between January 1, 2006, and January 1, 2019, that captures the burden of HIV, both prevalence and incidence estimates, HIV prevention and treatment cascades, key population size estimates, experienced violence, consistent condom use, and engagement with healthcare systems for female sex workers, men who have sex with men, people who use drugs, transgender people, and incarcerated populations. A team of reviewers will use Covidence to conduct two independent reviews of both title/abstract and full text for each article. REDCap will be used for data abstraction and storage.DiscussionFindings from this systematic review and the development of the enhanced graphical interface to display data, along with ongoing efforts to build capacity among key stakeholders to better use and interpret available data, will help ensure that available epidemiologic data related to key populations can be appropriately used to guide large-scale HIV funding and programmatic responses.Systematic review registrationPROPSERO CRD42016047259.Electronic supplementary materialThe online version of this article (10.1186/s13643-018-0894-3) contains supplementary material, which is available to authorized users.