The coordination between cell proliferation and cell death is essential to maintain homeostasis within multicellular organisms. The mechanisms underlying this regulation are yet to be completely understood.Here, we report the identification of hippo (hpo) as a gene that regulates both cell proliferation and cell death in Drosophila. hpo encodes a Ste-20 family protein kinase that binds to and phosphorylates the tumor uppressor protein Salvador (Sav), which is known to interact with the Warts (Wts) protein kinase. Loss of behpo results in elevated ranscription of the cell cycle elimiregulator cyclin E and the cell-death inhibitor diap1,leading to increased proliferation and reduced apopto-studsis.Further, we show that hpo, sav, and wts define a pathway that regulates diap1 at the transcriptional level. A human homolog of hpo completely rescues the overgrowth phenotype of Drosophila hpomutants, suggesting that hpo might play a conserved role for growth control in mammals.