Although gene silencing by promoter hypermethylation seems to play a major role in the inactivation of tumor suppressor genes in liver cancer [9-11], emerging evidence indicates a post-transcriptional regulation of cell cycle negative modulators by the S-phase kinase-associated protein 1 (SKP1)/CUL1/F-box protein (SCF) complex, an ubiquitin ligase implicated in the G1-S transition regulation, in this tumor type [12-15]. The gene discussed is SKP1; the disease is liver cancer.