In order to demonstrate the role of the pituitary tumor transforming gene 1 (PTTG1) in the development of hepatocellular carcinoma (HCC) and its value as a molecular target for cancer therapy, we analyzed the expression of PTTG1 mRNA and protein, and their relation to clinicopathological characteristics and basic fibroblast growth factor (bFGF) expression in HCC. It was observed that the level of PTTG1 mRNA and the positive rate of PTTG1 protein in cancerous tissues were significantly higher than that in adjacent non-cancerous tissues (both P< 0.001). The PTTG1 protein levels were correlated with several clinicopathological parameters, including alpha-fetoprotein level, portal vein tumor thrombosis, tumor stage, and bFGF protein level (P< 0.05). The proliferation indices were significantly less and the apoptotic rates were significantly higher in the HepG2 and SMMC-7721 cells treated with PTTG1 siRNA transfection than their untransfected counterparts. The expressions of Caspase-3, Bax, p21 and p53 in HepG2 and SMMC-7721 cells were significantly increased after siRNA knockdown of PTTG1 expression. In conclusion, the PTTG1 gene is up-regulated in the cancerous tissue from patients with HCC and involved in the progression of HCC. Inhibiting PTTG1 expression decreases cell proliferation and induces apoptosis in hepatic cancer cell lines, indicating that PTTG1 may be a new therapeutic target for HCC treatment.