Heparanase (hep) degrades heparan sulphate proteoglycans (HSPGs), which are the main components of the extracellular matrix. This process has been considered as the first step of tumour invasion or metastasis. However, HSPGs play an important role in signal transduction. Thus, the degradation of HSPGs by hep may suppress tumour cell growth. In the present study, we investigated the clinicopathological importance of enhanced hep mRNA expression in 48 hepatocellular carcinomas (HCCs) and in 48 non-cancerous liver samples obtained from the same patients by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). Spontaneous apoptosis in the hepatocytes was evaluated by immunohistochemistry. The relative hep mRNA expression levels were described as hep/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ratios. The hep mRNA levels of HCCs were significantly lower than those of non-cancerous livers (P<0.001). Hep mRNA levels decreased with increasing liver fibrosis. A significant positive correlation between hep gene expression and spontaneous apoptosis was detected. Hep expression in the tumours did not correlate with tumour differentiation or with tumour stage. However, low hep gene expression was associated with a poor disease-free survival of the patients. Thus, hep gene expression may play an important role in programmed cell death and this gene expression may be lost during the malignant transformation of hepatocytes.