Background Hepatitis C virus (HCV) infection remains a major public health concern for many countries. A recent survey report in Ghana revealed a national HCV prevalence rate of 4.6% in a population of 35 million but with notably higher regional variations ranging from 8.6 to 14.4%. Considering that Ghana is targeting micro-elimination of HCV as part of the STOP Hepatitis C project, it is prudent to estimate the current epidemiological burden of hepatitis C for evidence-based policymaking, public health research, and program direction. An initial search of the literature showed a previous review that spanned from 1995 to 2015. The gap of almost 10 years may not reflect the current burden of hepatitis C in Ghana, hence this review. A systematic literature search will be performed in the major electronic databases and search engines including PubMed, Embase, Web of Science, CINAHL, and African Journals Online (AJOL). There will be a search for articles reporting on the prevalence of hepatitis C in Ghana from 2016 to 2024 in these databases. The protocol is registered with PROSPERO (CRD42024592505).