Back ground: The prognosis of HCC is generally most serious with a great need for serum markers that could be used for its early detection and, consequently, to start a therapeutical procedure as soon as possible, potentially at a curable phase.Aim of work: to determine the value of serum level of soluble TNF - receptor II in the diagnosis and early detection of HCC in patients with chronic HCV infection. Patients and methods: The study was performed on 40 patients with chronic HCV infection.Results: We found that the serum level of sTNFR-IIα is significantly higher in HCC patients in comparison to the other groups. Our preliminary data revealed that exclusion of HCC among HCV infected patients with cirrhosis could be predicted when sTNFR-IIα is assessed at a cutoff value ≥ 250 pg/ml . Also, we found a positive correlation between the serum levelof sTNFRIIα and AST and ALT levels in Chronic non cirrhotic HCV infected patients with elevated enzymes .Conclusion: Occurrence of HCC among HCV infected patients with cirrhosis could be predicted when serum level of sTNFR-IIα was assessed at a cutoff value ≥ 250 pg/ml. It is recommended to carry out further studies with a larger sample size to underline the accuracy of our findings before their application at the population level.