To the best of our knowledge, in this study, we demonstrated for the first time that, silencing SAPCD2 activated the Hippo signaling in fibrosarcoma cells, as indicated by the reduced luciferase reporter activity of HOP-Flash, decreased nuclear expression of YAP and TAZ, decreased expression levels of multiple downstream genes of the Hippo pathway, and increased expression levels of p-MST1 and p-LATS1 in fibrosarcoma cells. This evidence concerns the gene YAP1 and fibrosarcoma.