This result demonstrated that the key component, RASSF1, in Hippo signaling is the prime target of SKP1 that mediates the stimulatory effect of SKP1 on YAP activity as well as colorectal cancer stemness, which indicated that both SKP1 and YAP inhibitor could be effective strategies for eradicating CRC-SCs. Here, RASSF1 is linked to colorectal cancer.