Hepatocellular carcinoma (HCC) is one of the most common types of tumors of the digestive system. Recent studies have established that keratin 19 (K19) positive HCC is associated with the malignant biological behaviors such as early metastasis, poor differentiation and higher aggressiveness. For better understanding the role of K19 in cancer stem cells, angiogenesis, invasiveness and apoptosis of HCC and its relevant impacts, the authors address the biological actions of K19 in HCC.