The Yes-associated protein (YAP) transcriptional co-activator is a key regulator of organ size and a candidate oncogene amplified in human cancers.YAP is inhibited by the Hippo tumor suppressor pathway through phosphorylation on multiple residues.TEAD family transcription factors directly bind to YAP and mediate YAP-induced gene expression.Here we report the three dimensional structure of YAP (residues 50-171)-TEAD1 (residues 194-411) complex, in which YAP wraps around the globular structure of TEAD1 and forms extensive interaction via three highly conserved interfaces.We show that the interface three including YAP residues 86-100is most critical for the complex formation.Our study reveals the biochemical nature of YAP-TEAD interaction and provides a basis for pharmacological intervention of YAP-TEAD hyperactivation in human diseases.