Matrix metalloproteinases (MMP) play an important role in tumor cell invasion and metastasis. We examined the expression of MMPs in hepatocellular carcinoma (HCC) to determine whether they may help indicate the progression of HCC and patient outcome. The expression of MMP-1, -2, -7, -9, and MT1-MMP were determined in 37 pairs of HCC and adjacent non-tumor tissue specimens by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). The tumor to non-tumor (T/N) ratios for mRNA expression of each MMP were compared with the clinicopathological findings and two-year disease-free survival rates. Immunohistochemical analysis for MMP-1 and -9 was performed in 30 specimens. MMP-1 and -9 expression was significantly higher in tumor tissue than in non-tumor tissue (p=0.001 and 0.0078, respectively). By contrast, the expression of MMP-2 and -7 was significantly lower in tumor tissue than in non-tumor tissue (p=0. 003 and 0.03, respectively). A higher MMP-9 T/N ratio was significantly associated with small HCCs (/=20 ng/ml) (p=0.013 and 0.028, respectively). Immunohistochemical analysis suggested that well differentiated HCC showed stronger immunoreactivity for MMP-9 than moderately differentiated HCC. MMP T/N ratio was not significantly associated with the disease-free survival rates. Overexpression of MMP-9 mRNA (T/N ratio >/=2) may be associated with the progression of small HCC (