Nuclear speckle-type pox virus and zinc finger protein (SPOP), a representative substrate-recognition subunit (SRS) of cullin-RING E3 ligase 3 (CRL3, a member of the CRL complex family), has been recognized to play a dual role in the development and progression of human cancers, including lung, colon, gastric, prostate and liver cancers [10–16]. Here, SPOP is linked to liver cancer.