The Yorkie homologues YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif， also known as WWTR1)， effectors of the Hippo pathway， have been identified as mediators for mechanical stimuli. However， the role of YAP/TAZ in haemodynamics-induced mechanotransduction and pathogenesis of atherosclerosis remains unclear. Here we show that endothelial YAP/TAZ activity is regulated by different patterns of blood flow， and YAP/TAZ inhibition suppresses inflammation and retards atherogenesis. Atheroprone-disturbed flow increases whereas atheroprotective unidirectional shear stress inhibits YAP/TAZ activity. Unidirectional shear stress activates integrin and promotes integrin-Gα interaction， leading to RhoA inhibition and YAP phosphorylation and suppression. YAP/TAZ inhibition suppresses JNK signalling and downregulates pro-inflammatory genes expression， thereby reducing monocyte attachment and infiltration. In vivo endothelial-specific YAP overexpression exacerbates， while CRISPR/Cas9-mediated Yap knockdown in endothelium retards， plaque formation in ApoE mice. We also show several existing anti-atherosclerotic agents such as statins inhibit YAP/TAZ transactivation. On the other hand， simvastatin fails to suppress constitutively active YAP/TAZ-induced pro-inflammatory gene expression in endothelial cells， indicating that YAP/TAZ inhibition could contribute to the anti-inflammatory effect of simvastatin. Furthermore， activation of integrin by oral administration of MnCl reduces plaque formation. Taken together， our results indicate that integrin-Gα-RhoA-YAP pathway holds promise as a novel drug target against atherosclerosis.