PTPN11,which encodes tyrosine phosphatase Shp2,is a critical gene mediating cellular responses to hormones and cytokines.Against original prediction as tumor suppressor for tyrosine phosphatases,PTPN11 was first identified as a proto-oncogene because activating mutations of this gene are associated with leukemogenesis.However,most recent experimental data suggest PTPN11/Shp2 acting as a tumor suppressor in hepatocarcinogenesis.This review focuses on the tumor-promoting or suppressing roles of the gene PTPN11/Shp2 in different cell types.