Abstract： Objective To study the expression of Shp2 in liver cancer stem cells and the significance of liver stem cells regulation,and then clarify the molecular mechanism of Shp2 in regulating the liver cancer stem cells,explore its feasibility as a therapeutic target for liver cancer and liver cancer biomarkers for individualized treatment.Methods Real-time PCR was used to detect the expression of Shp2 in chemotherapy resistant in HCC cells xenografts.In addition,the expression of Shp2 was detected by real-time PCR technique in stem cell enriched HCC cells using a variety of sorting techniques.The interfering Shp2 cell line was used to define the possible regulation mechanism of Shp2 on liver cancer stem cells by Western blot method.Results In vivo experiments showed that Shp2 expression increased in chemotherapy resistant liver cancer xenografts.What′s more,in vitro experiments,the expression of Shp2 was elevated in the liver cancer stem cells.The expression of Shp2 is closely related to the b-catenin in the interfering Shp2 HCC cell lines,suggesting that Shp2 may promote the formation of liver cancer stem cells through the Wnt/b-catenin pathway.Conclusion In this study,we found that the activation of Wnt/b-catenin signaling pathway by Shp2 in HCC cells promotes cancer stem cell expansion,which suggesting that Shp2 maybe as a biomarker of liver cancer stem cells,and provide a new molecular target and clinical basis for clinical transformation study.