Objective: Early finding of hepatocelular carcinoma (HCC) and monitoring of its metastasis are of the utmost importance. The objectives of this study were to investigate the values of circulating hepatoma-specific gamma-glutamyl transferase (HS-GGT) fraction and α-fetoprotein mRNA (AFP-mRNA) from peripheral blood mononuclear cels (PBMCs) in diagnosis or monitoring metastasis of HCC.Methods: Total RNA was extracted from hepatomas or PBMCs of patients, synthesized to AFP-cDNA through random primers and reverse transcriptase, amplified by using a nested PCR assay, and confirmed by sequencing. Simultaneity, the HS-GGT activities were quantitatively determined in sera of patients. The com-prehensive assessments of two markers were investigated in HCC patients.Results:The amplified fragments of AFP-mRNA were identical to original designed ones (159 bp) and confirmed by sequencing. The lowest sensitivity was 2 ng/L of total RNA. The incidences of AFP-mRNA and HS-GGT were 60.4% (113 of 187) and 84.5% (158 of 187) in the HCC group, and their significantly higher (P < 0.01) than that in any of other groups. The high frequencies of HS-GGT and AFP-mRNA were 78.2%and 56.4% in the HCC patients with AFP < 50 ng/mL. Al positive of AFP-mRNA was found in HCC patients with extrahepatic metastasis. No significant correlation was found between tumor size and AFP-mRNA or HS-GGT. The total incidence of com-bined AFP-mRNA and HS-GGT detection was 93.6 % for HCC diagnosis.Conclusion: HS-GGT and AFP-mRNA are specific markers for HCC diagnosis or diferentiation, especialy the former for early finding and the later for monitoring metastasis of HCC.