Abstract: Tumor stem cells point to the malignant subgroup of tumor tissue which have high invasiveness, multidrug resistance and are more likely to migrate, which was considered closely related to tumor recurrence. Hence, cancer stem cells may become the target of chemical therapy in the near future. CD133, CD90, CD44 were reported as the signature of cancer stem cells in several kinds of tumors. Besides being involved into the development of several organs, SOX9 (sex determining region Y box9) was reported to be closely engaged into tumor genesis and tissue fibrosis. Especially, its high expression can be found in many sorts of tumor stem cells. SOX9 is highly expressed in hepatocellular carcinoma and it has influence on the refresh, growth and drug resistance of the cancer stem cells through certain pathways. Therefore, SOX9 is a potential marker to evaluate the prognosis of HCC patients and therapy target.