Mechanistically, EM2 enhances the kinase activity of MST1/2 and increases its phosphorylation to activate the Hippo signaling pathway, resulting in the down‐regulation of oncofactors such as CTGF and CYR61, thereby inhibiting the proliferation of NSCLC cells and inducing cell senescence. Here, CCN1 is linked to non-small cell lung carcinoma.