Transforming growth factor beta-1 (TGF-beta-1) is a multifunctional cytokine involved in the regulation of growth and differentiation of both normal and transformed cells. The main aim of this study was to determine whether TGF-beta-1 or alpha fetoprotein (AFP) or the combination of the two is a better indicator for hepatocellularcarcinoma (HCC). Serum TGF-beta-1 and AFP were measured by ELISA in 40 healthy subjects, 23 patients with hepatocellular carcinoma (HCC), 70 patients with hepatitis B, 26 patients with hepatitis C and 16 patients with liver cirrhosis (LC). Patients with liver diseases showed significantly higher serum TGF-beta-1 values (> 3 fold) compared to control subjects. As for serum AFP, significant elevation was only observed for HCC cases. Serum TGF-beta-1 exhibited higher percent sensitivity compared to serum AFP in all liver diseases. Combination of serum TGF-beta-1 and AFP increased specificities in all cases studied. In conclusion, serum TGF-beta-1 is a more sensitive marker for HCC when compared to serum AFP and its specificity is increased when combined with serum AFP.