Objective: To investigate the status of hematogenous spreading of hepatocellular carcinoma (HCC) before or after surgical treatment or transcatheter arterial chemoembolization (TACE) and to elucidate the significance of peripheral blood Alphafetoprotein (AFP) mRNA expression in predicting recurrence or metastasis of HCC. Methods: Peripheral venous bloods were collected from 60 patients with HCC,20 of whom had received TACE before blood samples were collected, and from 30 subjects as control (10 cases with benign liver disorders, 20 healthy donors). AFP cDNA was amplified from 5 ml whole blood by nested reverse transcription polymerase chain reaction (RTPCR). Results: Of the 60 patients with HCC, 32 cases (53.3%) had positive AFP mRNA in their peripheral blood. In 33 patients with intra-and/or extrahepatic metastasis, 27 (81.1%) were positive for AFP mRNA. In patients who didnt yet have metastasis when samples were collected, 11 (29.7%) gave positive AFP mRNA, 6of whom developed tumor recurrence or metastasis after the samples were collected. The presence of AFP mRNA correlated with the stage of HCC and the presence of intrahepatic and/or extrahepatic metastasis, but did not correlate with tumor size and serum AFP level. There was no significant difference in AFP mRNA expression before and after surgical treatment or TACE.Conclusion: Detection of AFP mRNA by PCR provides a sensitive and specific assay of hematogenous dissemination of HCC. TACE can not prevent metastasis of HCC. Systemic chemotherapy or immunotherapy is needed to prevent occult or overt metastasis.