Abstract: Objective: To study the factors causing different biological behaviors between SHCC (small hepatocellular carcinoma) and LHCC (large hepatocellular carcinoma) and, to furthermore explore the results of possible mechanisms in these differences. Methods: The expression of nm23-H1, c-Met, MT1-MMP (membrane- type1 matrix metalloproteinase) and Ki-67 protein in 40 cases of SHCC and 53 cases of LHCC were studied by means of immunohistochemistry. Moreover, the relationship between protein expression and clinicopathological factors of hepatocarcinoma was analyzed. Results: The protein expression of nm23-H1, c-Met, MT1-MMP in SHCC differed from that in LHCC remarkably (P= 0.005, P=0.008 and P=0.007 respectively). The protein expression of nm23-H1 has a negative correlation with distant metastasis of the tumor (P=0.041). On the other hand, the protein expression of c-Met and MT1-MMP has a positive correlation with tumor invasion and distant metastasis (P<0.05). Conclusion: As a result of alteration of nm23-H1, c-Met, MT1-MMP protein expression in the process of tumor progression, the prognosis of LHCC is poorer than SHCC.