Among the drugs that play a multiple action on factors and pathways that drive angiogenesis, such as VEGFR1–3, PDGFRα, RET, KIT, lenvatinib has been proposed for patients in first line treatment and non resectable HCC, whereas cabozantinib represents a valid option for second-line treatment patients with advanced HCC. This evidence concerns the gene FLT1 and hepatocellular carcinoma.