These results suggest that (a) cyclin D1 indeed interacted with Smad2/3 and Smad4 in vitro; (b) cyclin D1 expression enhanced Smad2/3 phosphorylation and Smad4 expression in liver cancer cells; (c) cyclin D1 may mediate liver CSC features via TGF-β/Smad signaling, a critical pathway for self-renewal. This evidence concerns the gene CCND1 and liver cancer.