In many countries with high HIV prevalence, there exists extensive stigma and discrimination against sexual minorities. In South Africa, national HIV prevention programs have largely failed to tailor HIV testing services to these marginalized, key populations, including Men who have Sex with Men (MSM). As a result, MSM have some of the highest HIV prevalence estimates in the country (33.9%) and are not testing at rates commensurate with their risk. HIV self-testing (HIVST) offers a convenient and private method for MSM to attain regular, frequent HIV testing, to ultimately improve the number of men aware of their status and in care. However, there have been few studies investigating HIVST uptake, usage frequency, and linkage to care in this population. Furthermore, there are no mathematical models examining the potential impact of introducing HIVST among MSM to inform policy makers’ decisions. With data from one of the first HIVST studies undertaken with MSM in South Africa and a large surveillance study of over 3000 MSM in the South African Health Monitoring Survey (SAHMS), we will develop a mathematical model to examine the potential impact of HIVST on the South African epidemic within the MSM community. This dynamic transmission model will estimate projections of HIV incidence under scenarios with and without HIVST, providing a quantitative measure of the potential impact of HIVST for MSM. The model will measure the potential of the intervention to prevent new infections and HIV-related deaths, through earlier treatment uptake and protective sexual behaviors. We will evaluate the cost-effectiveness of the HIVST program as an incremental cost per disability-adjusted life-year (DALY) averted compared with the current clinic-based testing scenario. These outcomes will enable local and national policy makers to assess the potential for HIVST and offer guidance to ensure optimal provision of programs to the MSM community.