Hepatitis C virus (HCV) is implicated in carcinogenic infections like hepatocellular carcinoma (HCC). Given that no HCV vaccine is currently available, comprehensive epidemiological understanding is crucial for devising effective prevention strategies. In North Africa, existing data on HCV infection and HCV-associated HCC are frequently outdated or limited to specific populations. This systematic review aims to offer new insights into the epidemiology of HCV infection, HCV genotype distribution, and HCV-related HCC in this region. We collected data from electronic databases: PubMed, ScienceDirect, ResearchGate, Google Scholar, and public health reports between 1989 and 2023. We reported the studies carried out in each country in general populations and in groups exposed to HCV infection. Our results show that HCV prevalence varies from 0.5% to 4.61% among the general populations in North African countries. HCV genotype 1 remains the most dominant in the Greater Maghreb region, while genotype 4 is the most dominant in the Nile Valley region. HCC incidence varies between the five countries, and HCV is responsible for 60% of cases, with male dominance. Egypt had the highest number of deaths from HCV-associated HCC. Other factors such as HBV, diabetes, and alcohol use are also responsible for HCC in North Africa. Urban growth and socioeconomic changes have impacted HCV prevalence in the North African region, especially among rural populations, and introduced new risks, such as coinfections and Type 2 diabetes. Here, we propose some recommendations for HCV control and management by patient category in North Africa.