Heparanase plays an important role in invasion and metastasis of tumor cells. In this study, we explored the expression and clinicopathological significance of heparanase protein in hepatocellular carcinogenesis to investigate their roles in invasion and the relationship between biological behavior and prognosis of hepatocellular carcinoma (HCC) in tissue microarrays (TMAs). Heparanase expression was examined by immunohistochemistry in TMAs comprising 120 cases of HCC, 48 cases of adjacent tumor liver, 62 cases of cirrhosis, and 23 cases of normal liver tissues. Statistical analyses were determined to access the correlation between heparanase expression and the clinicopathological features of HCC. The results showed a positive level of heparanase in HCC tissues that was significantly higher than that in adjacent tumor liver, cirrhosis, and normal liver tissue. Heparanase was expressed lower in clinical TNM stages I and II than in III and IV. Moreover, the expression of heparanase in cases without metastasis within 20 months was statistically lower than in those with metastasis. Furthermore, heparanase expression in groups of alpha-fetoprotein (AFP) > or = 400 microg/L, portal vein tumor emboli, multiple tumor nodes, and tumor diameter > or = 5 cm were significantly higher than those of corresponding groups, while it was not associated with patients' age, sex, histological classification, cirrhosis, or tumor capsular infiltration. In conclusion, TMA is a powerful tool for the rapid identification of molecular alterations in HCC. The overexpression of heparanase may play an important role in hepatocarcinogenesis, progression, and metastases of HCC. It could serve as a determining factor for clinical prognosis and curative effect.