Cancer continues to be the leading cause of death worldwide. Hepatocellular carcinoma (HCC), a prominent form of liver cancer, is the second leading cause of cancer-related deaths, thanks to the lack of efficient diagnostic tools and consequently late diagnosis and to the scarce of available suitable treatments. Thus, novel approaches to treat HCC are in demand. The fast-growing field of nanotechnology offers infinite possibilities to design materials in the nanoscale with unique properties due to their high surface area and small size. Nanotechnology enabled scientists to design drug delivery systems that serve multiple purposes including treatment, diagnostics and imaging. This review provides an update on the overall concept and potential of cancer nanotechnology; highlights the advances made particularly toward therapeutic nanomaterials targeting HCC. Obstacles hindering further development of nanomaterials -mediated cancer therapy will also be discussed.