The identification and characterization of hepatic stem cell compartments is the key to resolving clinical disorders and diseases in the liver. Hepatoblasts (or early fetal hepatocytes) fulfill several criteria of hepatic stem cells during liver development. Unlike mature hepatocytes, immature fetal hepatocytes can proliferate autonomously in the absence of any growth factors in vitro. However, the regulation of fetal hepatocyte proliferation remains unclear. Recently, we identified a novel factor, hepatoma-derived growth factor (HDGF), from the human hepatoma-derived cell line HuH-7, which autonomously proliferate in serum-free defined medium. Here, we focus on the functional roles of HDGF, and review several molecules involved in the growth regulation of hepatocytes in the immature stage.