One of the key questions in developmental biology is how tissue growth is controlled to give rise to organs of specific sizes and shapes. Although some genes and pathways involved in the genetic and environmental control of tissue growth have been uncovered, the understanding of this process remains incomplete. In order to find new regulators of growth we carried out an in vivo RNAi screen in the Drosophila wing. I participated in the validation of candidate genes from the screen and identified the mask gene as an essential regulator of tissue growth acting in the Hippo signaling pathway. This pathway acts via the Yorkie (Yki)/Yes-associated protein (YAP) transcriptional co-activator to control tissue growth in both Drosophila and mammals. Yki/YAP translocates from the cytoplasm to the nucleus to activate target genes, a process that is negatively regulated by the Warts kinase, one of the core components of the Hippo pathway. I found that Mask is an essential positive regulator of Yki acting downstream of Warts. Mask is required for normal tissue growth, for the expression of Yki target genes and for the overgrowth phenotype caused by Yki overexpression. Mask binds to Yki and the two proteins translocate from the cytoplasm to the nucleus together in response to various stimuli. My results show that Mask acts in the nucleus to promote Yki target gene activation. Finally, Mask’s function appears to be conserved in humans, as two human homologues of Mask (hMask1 and hMask2) translocate with YAP to the cytoplasm upon cell contact inhibition, and we demonstrate that one of these homologues promotes YAP’s transactivation function.