Although liver disease-associated TGF-β signaling is exhibited by all different cell types in the liver, such as stellate cells, Kupffer cells and hepatocytes,2 HCC was recently reported to arise exclusively from hepatocytes.8 Thus, we decided to further evaluate the functional role and mechanistic background of SMAD7 in DEN-induced mouse HCC by hepatocyte-specific gain and loss of SMAD7 expression. Here, SMAD7 is linked to liver disorder.