The liver is an organ known to have tremendous regenerative capacity. Liver pathologies affect millions of patients worldwide. Stem cells are promising tools as a regenerative medicine for the treatment of degenerative disorders, inborn errors of metabolism, and organ failure. Although stem cells have a desired role in treatment of various diseases, it has an undesirable role in generation and progression of tumor cells. Under the right conditions in the body or laboratory, stem cells divide to form more cells called daughter cells. Hematopoietic stem cells (HSCs) are the predominant population of stem cells within bone marrow and express CD34 as the cell surface marker; they can renew themselves and differentiate into progenitor cells. Mesenchymal stem cells (MSCs) are a rare population in bone marrow which is capable of self-renewal and differentiation into hepatocytes-like cells as well as cell types of mesenchymal origin. MSCs based therapy has been suggested as an attractive therapeutic option for treatment of liver cirrhosis and fibrosis due to immune modulatory properties. On the other side, liver cancer stem cells (LCSC) have an important role in occurrence and development of liver cancer as in hepatocellular carcinoma. The development of cancer recurrence, metastasis, and chemo- and radioresistance in a solid tumor is attributed to the presence of CSCs. Accumulating evidence demonstrated the existence of a small subset of cancer cells with stem cell properties and several cancer stem cells (CSCs) markers have been identified. Therapies targeting these cells may have great potential for clinical treatment and prognosis of liver cancer result in eradication of liver CSCs. Therefore, the aim of this study is to focus on the recent advances in understanding of the biology of liver CSCs, and the development of strategies for their treatment.