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. The gene discussed is FGF2; the disease is hepatocellular carcinoma.