Abstract: Objective: To investigate the midkine protein expression in human hepatocellular carcinoma (HCC) and its relation to cancer cell blood dissemination. Methods: Circulating tumor cells were detected in preoperative blood samples using reverse transciption polymerase chain reaction (RT-PCR) for alpha-fetoprotein (AFP) mRNA. Midkine expression was immunohistochemically examined on surgically resected HCC tissues. Results: Fortyone HCC patients with serum AFP positive were studied.Positive AFP mRNA expression was showed in 18 preoperative blood samples (43.9%) and midkine overexpression was detected in 29 excised tumors (70.7%). Among the 29 patients, 18 (62.1%) showed AFP mRNA positive in their preoperative blood samples. In contrast, the positive AFP mRNA expression was only observed in 3 out of 12 patients (25.0%) without aberrant midkine expression. Statistical analysis showed that abnormal midkine expression in the tumors was a varial significantly associated with the presence of tumor cells in the blood circulation (P<0.05). Conclusion: In human hepatocellular carcinoma, midkine overexpression is correlated with a haematogenuous spread of the primary tumor cells, may be a marker of tumor metastatic potential.