Abstract: Aims/Background: Transforming growth factor-α (TGF-α) is a potent mitogen of normal and neoplastic hepatocytes. In addition, TGF-α has been reported to play a pivotai role in hepatocarcinogenesis. To evaluate the significance of TGF-α in chronic liver diseases and hepatocellular carcinoma, we examined serum TGF-α, and expression of TGF-α, epidermal growth factor receptor (EGFR) and proliferating cell nuclear antigen (PCNA) mRNA in liver tissues. Methods: Thirty-five patients with chronic hepatitis (CH), 33 with liver cirrhosis (LC), 55 with hepatocellular carcinoma (HCC) and 53 normal controls (C) were enrolled in this study. Serum TGF-α levels were measured by an enzyme-linked immunosorbent assay. Expression of TGF-α, EGFR, PCNA and β-actin mRNA in liver tissues were examined by reverse transcription polymerase chain reaction. Results: Serum TGF-α levels in C, CH, LC and HCC were 5.6 ± 2.1. 33.2 ± 8.3, 404.0 ± 173.0 and 100.3 ± 39.2 pg/ml, respectively. Serum TGF-α level in LC was higher than in other diseases (p < 0.01, compared to CH, HCC and C, respectively). Serum TGF-α levels exhibited a significant positive correlation with total bilirubin, ICGR15 and Pugh score (p < 0.01, p < 0.01 and p < 0.05, respectively), and increased in parallel with severity of disease according to Child classification. Although the ratios of TGF-α, EGFR and PCNA mRNA to β-actin mRNA were not significantly different among the diseases, the TGF-α/β-actin ratio correlated with EGFR/β-actin and PCNA/β-actin ratios (p < 0.001 and p < 0.0001, respectively), and EGFR/β-actin ratio was related to PCNA/β-actin ratio in ail patients, especially with HCC. Conclusion: The results of the present study suggest that serum TGF-α levels are closely related to severity of liver dysfunction, and that hepatic expression of TGF-α and EGFR correlates with proliferation of normal and neoplastic hepatocytes.