Hepatocellular carcinoma is a serious human disease with fatal consequences. The most distressing aspect of hepatocellular carcinoma is the limited improvement in mortality (mortality rate of more than 90%). At present, the underlying molecular mechanisms are not well understood and treatment options are often of limited efficacy. This review presents our current understanding of the burden of hepatocellular carcinoma on human health, pathogenesis and pathophysiology, and molecular mechanisms associated with the disease, as well as our knowledge of the physical barriers, cellular mechanisms and molecular elements that may be targets for therapeutic interventions and/ or the development of preventative measures. As the proposed findings present a major risk to public health, it is hoped that robust intervention measures will be introduced for aflatoxins monitoring and reduction in diet.