Liver cancer (mostly hepatocellular carcinoma, HCC) is both common and highly lethal throughout Africa, in particular in Western and Middle Africa where HCC is the first cause of cancer death in men and the third in women. In these high-incidence areas, HCC develops mostly early (<50 years), with an aggressive clinical course and frequently without prior diagnosis of liver cirrhosis. The dynamics of African populations predict that the burden of liver cancers will be multiplied by three to four in the next decades unless effective prevention and therapy is achieved. This article outlines a path for significantly curbing the mortality of liver cancer in Africa by combining primary prevention, improved early detection and introduction of innovative and appropriate management strategies.