Yes-associated protein (YAP) plays a central role in the Hippo pathway, primarily governing cell proliferation, differentiation, and apoptosis. Its significance extends to tumorigenesis and inflammatory conditions, impacting disease initiation and progression. Given the increasing relevance of YAP in inflammatory disorders and cancer, this study aims to elucidate its pathological regulatory functions in these contexts. Specifically, we aim to investigate the involvement and molecular mechanisms of YAP in various inflammatory diseases and cancers. We particularly focus on how YAP activation, whether through Hippo-dependent or independent pathways, triggers the release of inflammation and inflammatory mediators in respiratory, cardiovascular, and digestive inflammatory conditions. In cancer, YAP not only promotes tumor cell proliferation and differentiation but also modulates the tumor immune microenvironment, thereby fostering tumor metastasis and progression. Additionally, we provide an overview of current YAP-targeted therapies. By emphasizing YAP's role in inflammatory diseases and cancer, this study aims to enhance our understanding of the protein's pivotal involvement in disease processes, elucidate the intricate pathological mechanisms of related diseases, and contribute to future drug development strategies targeting YAP.