Primary liver cancer, largely hepatocellular carcinoma (HCC), is the third most common cause of cancer death in the world; the overall five-year survival is only 3 percent to 5 percent [1]. Fifty-five percent of deaths occur in China [1]. Metastasis and primary tumor recurrence are the major causes of death. After curative resection (en bloc removal of tumor mass with margins free of tumor at resection), the five-year recurrence rate has been reported to be 61.5 percent, although it is lower (43.5%) after resection of small HCC tumors, which is mainly the result of intrahepatic metastasis via vascular invasion [2]. Because of the hypervascularity of the tumors, vascular invasion occurs in the majority of cases, and HCC metastases to lung, bone, adrenal gland, and other sites via the bloodstream are commonly encountered. Lymph node metastases, particularly in the hepatic hilar area, also occur with high incidence.

Studies of HCC metastasis during the past decades have included early detection and re-resection for subclinical recurrence after curative resection [3], establishment of a metastatic human HCC model system for screening novel therapeutic approaches [4–6], finding of a molecular signature with 153 genes and an immune response signature in the liver microenvironment that can also predict HCC metastasis [7–8], discovery of the association between chromosome 8p deletion and HCC metastasis [9], translation of several biomarkers for clinical prediction of HCC metastasis/recurrence [10–13], identifying novel markers for prediction and therapeutic target [14, 15], demonstrating the inhibitory effect of interferon-alpha on the metastatic recurrence of HBV-related HCC [16, 17], exploring other interventional agents [18–20], and optimizing radiotherapy for HCC metastasis [21, 22].