To date, the most successful clinical inhibitor of RAF activity is sorafenib (Nexavar, BAY 43-9006) [8]–[10], an orally available multi-targeted kinase inhibitor, that blocks the activation of C-RAF, B-RAF (both the wild-type and the activated V600E mutant), c-KIT, FLT-3, RET, vascular endothelial growth factor receptor 2 (VEGFR-2), VEGFR-3, and platelet-derived growth factor receptor β (PDGFR-β) [8]–[10], currently approved for the treatment of metastatic renal cell carcinoma (RCC) and for advanced hepatocellular carcinoma (HCC), and under investigation in other malignancies. This evidence concerns the gene BRAF and hepatocellular carcinoma.