Although the "cancer stem cell (CSC)" hypothesis was first proposed roughly 50 years ago, recent progress in stem cell biology and technologies has successfully achieved the identification of CSCs in a variety of cancers. CSCs are defined as a minor population which possesses a prominent ability to generate new tumors that faithfully reproduce the phenotype of original tumors in xenotransplant assays. Additionally, CSCs are able to self-renew and generate differentiated progenies to organize a hierarchical cell system in a similar fashion to normal stem cells. Although not all types of cancer follow the CSC theory, it provides an attractive cellular mechanism to account for the therapeutic resistance and recurrence of the disease. A minor population with CSC properties has been detected in a number of established hepatocellular carcinoma (HCC) cell lines and extensive analyses characterizing the CSC system in primary HCC samples are now ongoing. Considering that HCC has high rates of recurrence and mortality, novel therapeutic approaches are urgently required. Although the clinical relevance of CSCs remains elusive, deep understanding of the cellular organization of HCC may allow us to develop therapies targeting specific cell types such as CSCs.