The Hippo/Mst pathway is a signaling cascade that controls organ growth and regeneration. Hydra is a cnidarian freshwater polyp characterized by an amazing regenerative capacity, leading to the re-development of any missing body part. Components of the Hippo/Mst pathway are highly conserved in Hydra. In this study, we show that the Mst, LATS and 14-3-3 proteins are strongly expressed in fast cycling cells, i.e. pairs of interstitial stem cells and clusters of nematoblasts. We also show that the Hydra transcriptional coactivator YAP (hyYAP) can sense cell density. Indeed GFP-hyYAP expressed in human U2OS cells is cytoplasmic in high density cells but nuclear in those maintained at low density. Moreover Hydra Yap can rescue the human Yap function in U2OS cells, by up-regulating Cyclin-E, a target gene of the Yap/Tef complex. These results suggest that the human and Hydra Hippo/Mst pathways similarly control cell proliferation in response to cell density.