In this study, we found that cancer stem-like sphere cells enriched from human hepatocellular carcinoma cell line Hep G2 could differentiate into endothelial cells morphologically and functionally, and this process could be blocked by Akt1/2 kinase inhibitor and IKK-β inhibitor BAY 11-7082 but not by Bevacizumab, a VEGFA-binding antibody, and DAPT, a γ-secretase inhibitor. The gene discussed is AKT1; the disease is hepatocellular carcinoma.