Abstract Worldwide hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths with 80% of cases occurring in poor countries. In Africa HCC is the most common cause of cancer-related deaths in men and the third most common in women. Although HCC is prevalent in all Sub-Saharan African countries where data exist, the highest prevalences have been reported in countries in West Africa with annual incidences as high as 20 per 100 000 inhabitants. Historically viral hepatitis, in particular hepatitis B virus (HBV), aflatoxin and dietary iron overload have been implicated as the main etiological factors, but both alcoholic liver disease and metabolic syndrome-associated non-alcoholic fatty liver disease (NAFLD) seem to play an increasingly important role. There are striking differences in the clinical presentation, clinical course and prognosis of HCC in African patients, compared to developed countries. In African populations, in particular in rural areas, the disease occurs at a younger age with a mean age at presentation as low as 34.7 years having been reported. Furthermore, a larger percentage of HCCs present in non-cirrhotic livers. In well-resourced countries the diagnosis of cirrhosis would prompt tumour-directed investigations and screening for HCC with potentially earlier detection of tumours. This partially explains the fact that African patients present with larger tumours and more frequently with advanced disease in terms of metastatic burden. African patients are therefore less likely to undergo curative-intended intervention with resection rates as low as 1% being reported in rural African populations, compared to up to 37% in well-resourced Western countries. Whereas improved survival has been reported for patients undergoing curative-intended intervention in a number of well-resourced countries, the prognosis for African patients in general remains dismal with annual mortality rates approaching the annual incidence. The continent faces tremendous challenges in managing HCC. With virus-related HCC being responsible for approximately 90% of HCC cases, primary prevention with HBV immunization will have an immense impact on the occurrence of HCC. In spite of immunization having been shown to be cost-effective in low and middle income countries and a WHO recommendation that the HBV vaccine should be incorporated into the expanded program of immunization, the roll-out in Africa has been hampered by regulatory, financial, logistical, social and cultural barriers. Diagnostic capabilities, universally very limited in African countries, are typically concentrated in urban facilities, out of reach of rural patients. Access to treatment, whether curative- or palliative-intended is limited. It is a perverse coincidence that in the recently published report of The Lancet Commission on Global Surgery Western, Central and Eastern Sub-Saharan Africa were identified respectively as the regions with the highest, second highest and third highest rates of surgical need per population in the world. One can question whether there, on a global scale, is sufficient focus on the unique and often desperate fate of African patients. With some exceptions, mainstream HCC initiatives are exclusive, or are perceived as being exclusive of African institutions. This is ominously evident in the fact that less than 1% of currently ongoing clinical HCC trials are conducted on the continent, in spite of Africa being one of the hotbeds of HCC. Citation Format: Eduard Jonas. The scourge of hepatocellular cancer in Africa [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA24.