To further investigate the molecular mechanism of hSulf-1 effect on cancer cell cycle and apoptosis, we found that the reactivation of hSulf-1 expression and function in hSulf-1-negative HCC cell lines can downregulate the phosphorylation of AKT and ERK and inhibit the activity of bFGF-induced AKT and ERK signaling in HCC cells, then finally led to cell cycle arrest and cell apoptosis by suppressing the expression of Cyclin D1. This evidence concerns the gene CCND1 and hepatocellular carcinoma.