Hippo signaling pathway inactivation (HPI) is frequently identified in malignant mesothelioma (MM). Statin induces YAP phosphorylation in MM cells via mevalonate pathway. CD44 expression is regulated by YAP at the transcriptional level. CD44 also induces HPI status through Merlin according to cell density. Statin attenuates CSC-like properties through YAP/CD44 suppression in MM.