Aim: To investigate the role of transforming growth factor-β (TGF-β) derived from regulatory T cells in metastasis of hepatocellular carcinoma. Methods: Forty-eight primary liver cancer patients without metastasis, 32 liver cancer patients with distant metastasis (17 cases of lung metastasis and 15 cases of brain metastasis), and 54 healthy subjects were included in this study. Serum concentrations of interleukin-10 (IL-10), IL- 17A, tumor necrosis factor-α (TNF-α) and TGF-β were measured by ELISA. Levels of TGF-β in peripheral blood mononuclear cells (PBMCs) and regulatory T cells were determined by flow cytometry and RT-PCR, respectively. Results: Serum levels of TNF-α and TGF-β were significantly increased in liver cancer patients with metastasis compared with normal controls. Serum level of TGF-β was significantly higher in liver cancer patients with metastasis than in liver cancer without metastasis and normal controls (both P < 0.05). Furthermore, we confirmed that TGF-β in liver cancer patients with metastasis was derived from regulatory T cells by quantitative real-time PCR and flow cytometry. Conclusion: TGF-β has a dual role in tumorigenesis; it acts as a tumor suppressor in early stage but promotes tumor cell invasion and metastasis in advanced stage. High level of TGF-β was found only in liver cancer patients with metastasis. © 2013 Baishideng. All rights reserved.