The presence of circulating tumor cells (CTCs) in patients with hepatocellular carcinoma (HCC) suggests metastasis to extra-hepatic organs. Snail is a key regulator of epithelial mesenchymal transition, which is closely associated with tumor metastasis. The aim of this study was to investigate the presence of CTCs and evaluate the significance of Snail mRNA levels in peripheral blood of HCC patients with and without extra-hepatic metastasis. Sixty-six consecutive patients with HCC (30 without metastasis, 36 with metastasis) were prospectively enrolled, as were 30 with liver cirrhosis and 23 healthy subjects. CTCs were isolated by FACS using Ber-EP4 and anti-CD45 antibodies, and CTC identity confirmed by immunofluorescent cytokeratin staining. Snail mRNA levels were measured by quantitative real-time PCR of blood samples. CTCs, positive for pan-cytokeratin and Snail, were isolated from five HCC patients with metastasis. The mean amount of Snail mRNA in HCC with metastasis was 18.8-fold, 26.6-fold greater than HCC without metastasis, liver cirrhosis, respectively. When compared with healthy controls, the mean level of Snail mRNA in HCC without metastasis was 10.1-fold greater (P < 0.001). In six patients showing complete remission of HCC, Snail mRNA decreased to levels similar to those of healthy controls. This study suggests the possibility that circulating Snail mRNA levels may have been associated with extra-hepatic metastasis in HCC patients.