This article reviews mechanisms involved in development of hepatocellular carcinoma and how host and environmental factors interact at a molecular level to cause cancer. These processes are intimately linked with strategies for early detection since molecular intermediates on the carcinogenesis pathway can now be detected with increasing levels of sensitivity. Similarly host factors influencing response to environmental agents, together with substances produced by early cancers, can be assayed in fine detail with new and emerging technologies. These advances in the field of biomarkers may lead to more rapid diagnosis and ultimately to improved survival as novel therapeutic strategies are adopted.