The molecular mechanisms of organ size control and regulation remain one of the major unsolved mysteries of development biology.Almost a decade ago,the discovery of the Hippo signaling pathway in Drosophila shed some light on this puzzling issue.The Hippo signaling pathway is highly conserved in both invertebrates and vertebrates,and plays critical roles in animal development.It controls organ size and growth by inhibiting cell proliferation and by promoting apoptosis.Malfunction of the Hippo signaling pathway leads to cancer development and tumorigenesis.Although the core of the signaling pathway is well understood,the upstream inputs and downstream transcriptional regulation are still obscure to us.In this review,we summarize the current understanding of the mechanism and the function of the Hippo signaling pathway and compare its differences between flies and mammals.We underline the crosstalk between the Hippo signaling pathway and other signaling pathways,and the possible roles of the Hippo pathway in stem cell proliferation and self-renewal. The molecular mechanisms of organ size control and regulation remain one of the major unsolved mysteries of development biology. Almost a decade ago, the discovery of the Hippo signaling pathway in Drosophila shed some light on this puzzling issue. The Hippo signaling pathway is highly conserved in both invertebrates and vertebrates, and plays critical roles in animal development. It controls organ size and growth by inhibiting cell proliferation and by promoting apoptosis. Malfunction of the Hippo signaling pathway leads to cancer development and tumorigenesis. Although the core of the signaling pathway is well understood, the upstream inputs and downstream transcriptional regulation are still obscure to us. this summa, we summarize the current understanding of the mechanism and the function of the Hippo signaling pathway and compare its differences between flies and mammals. We underline the crosstalk between the Hippo signaling pathway and other signaling pathways, and the possible roles of the Hippo pathway in stem cell proliferation and self-renewal.