The aim of our study was to improve the detection of HCC by measuring alpha-fetoprotein (AFP) in addition to other molecular markers by estimating the plasma concentration of transforming growth factor beta (TGF-β) and epidermal growth factor receptor (EGFR). In particular, the role of hepatitis C and B viruses (HCV and HBV) infection was evaluated with relation to TGF-β and EGFR plasma concentration.Eighty-five patients with liver disease, 54 with hepatocellular carcinoma (HCC), 16 with liver metastasis (LM), 15 with liver cirrhosis (LC) and 30 healthy volunteers were evaluated. AFP, TGF-β and EGFR were detected with enzyme-linked immunoassay (ELISA) in plasma of all study participants.The mean values of TGF-β and EGFR in all patients were much higher than in control group, p<0.0001. In HCC patients the levels of TGF-β and EGFR were much higher than in LM and LC patients. Moreover, TGF-β and EGFR were significantly higher in the presence of both viruses or only in the presence of HCV, p=0.002. No decrease or increase of AFP was noted in these patients.Our data suggest the reliability of TGF-β and EGFR in detecting HCC, in particular when the carcinogenesis is affected by virus infection.