BACKGROUND: More than 40% of adults in Sub-Saharan Africa are unaware of their HIV status. HIV self-testing (HIVST) is a novel approach with a potential to increase uptake of HIV testing and linkage to care for people who test HIV positive. We explored HIV stakeholder's perceptions about factors that enable or deter the uptake of HIV self-testing and experiences of self-testing of adult users in Africa. METHODS: This systematic review of qualitative evidence included articles on qualitative studies published or made available between January 1998 to February 2018 on perspectives of key stakeholders, including HIV policymakers, HIV experts, health care providers, and adult men and women (18 years and above) about factors that enable or deter the uptake of HIV self-testing and experiences of self-testing among adult users. We searched CINAHL, MEDLINE in Pubmed, EMBASE, AJOL, PsycINFO, Social Science Citation Index (SSCI), and Web of Science for articles in English on HIVST with qualitative data from different African countries. RESULTS: In total, 258 papers were retrieved, and only nine (9) studies conducted in 5 African countries were eligible and included in this synthesis. Perceived facilitators of the uptake of HIVST were autonomy and self-empowerment, privacy, confidentiality, convenience, opportunity to test, including couples HIV testing, and ease of use. The perceived barriers included the cost of buying self-test kits, perceived unreliability of test results, low literacy, fear and anxiety of a positive test result, and potential psychological and social harms. HIV stakeholder's concerns about HIVST included human right issues, lack of linkage to care, lack of face-to-face counseling, lack of regulatory and quality assurance systems, and quality of self-test kits. Actual HIVST users expressed preference of oral-fluid self-testing because of ease of use, and that it is less invasive and painless compared to finger-stick/whole blood-based HIV tests. Lack of clear instructions on how to use self-test kits, and existing different products of HIVST increases rates of user errors. CONCLUSIONS: Overcoming factors that may deter HIV testing, and HIVST, in particular, is complex and challenging, but it has important implications for HIV stakeholders, HIVST users, and public health in general. Research is warranted to explore the actual practices related to HIVST among different populations in Africa.