The ligand insulin-like growth factor (IGF)-II is highly overexpressed in human hepatocellular carcinoma (HCC) and promotes tumour cell growth. Thus, this signalling axis is a prime target for potential anti-cancer therapies. In this context, gene-specific siRNA against IGF-signalling components as well as IGF1R selective receptor tyrosine kinase (RTK)-inhibitors (tyrphostins) may therefore offer new therapeutic options since both small interfering RNAs (siRNA) and small inhibitory molecules significantly reduce IGFIR signalling in HCC cell lines. However, since highly specific inhibition by siRNA is currently not applicable in the treatment of cancer, selective RTK-inhibitors represent the most promising approach for future therapeutic strategies.