Discoveries of oncogenic signaling molecules lead to the comprehension of molecular mechanisms of tumor progression, as well as to the development of novel therapeutic tools for hepatocellular carcinoma. We have identified critical functions of intracellular signals transmitted from insulin-like growth factor and Wnt oncoprotein in carcinogenesis. The insulin-like growth factor system activates a number of signaling cascades resulting not only in hepatic mitogenesis, but also in cell survival. The secreted oncoprotein Wnt transforms beta-catenin potentials as a component of cell adhesion complexes with cadherins, into a transcription factor in the nucleus. Here, the important role of such signal transduction is reviewed, and we emphasize its control as a promising approach for the treatment of hepatocellular carcinoma.