Currently, surgical resection is one of only a few options for treating hepatocellular carcinoma (HCC). Unfortunately, postoperative tumor recurrence remains almost inevitable despite additional radiation or chemotherapy treatment following radical resection. Clinical observations and a growing body of experimental evidence have led to speculation that there is a population of persistent hepatic cancer stem cells (HCSCs), which are difficult to completely remove surgically. HCSCs are most often in a quiescent state and thought to reside in a specific microenvironment known as a niche that provides the cues necessary for HCSCs to maintain a balance of self-renewal and differentiation. Residual HCSCs following surgery may alter their fate by invading into the blood circulation. Furthermore, it remains to be determined if hepatectomy render the postoperative niche more favorable for the survival and growth of HCSCs, and therefore the recurrence of HCC. A better understanding of the mechanisms for HCSCs self-renewal, invasion and recurrence may provide new insights into curative strategies for treating HCC. (C) 2013 Elsevier Ltd. All rights reserved.