Human cells can sense mechanical stress acting upon Integrin adhesions and respond by sending the YAP (YAP1) and TAZ (WWTR1) transcriptional co-activators to the nucleus to drive TEAD-dependent transcription of target genes. How Integrin signaling activates YAP remains unclear. Here we identify a key role for the Enigma (PDLIM7) and Enigma-like (PDLIM5) family of PDZ and LIM domain containing proteins in Integrin-mediated mechanotransduction. YAP binds to PDLIM5/7 via its C-terminal PDZ binding motif (PBM), which is essential for full nuclear localization and activity of YAP. Accordingly, silencing of PDLIM5/7 expression reduces YAP nuclear localization, tyrosine phosphorylation, and transcriptional activity. The PDLIM5/7 proteins are recruited from the cytoplasm to Integrin adhesions and F-actin stress fibres in response to force by binding directly to the key stress fibre component alpha-actinin. Thus, forces acting on Integrins recruit Enigma family proteins to trigger YAP activation during mechanotransduction.