Background and study aim: Most of the morbidity and mortality of chronic liver diseases is due to its progression and complication of cirrhosis as ascites. The cancer antigen (CA) -125 is a high molecular mass glycoprotein produced both by ovarian cancer cells as well as by normal cells derived from coelomic epithelium. This study was conducted to assess the serum and/or ascitic fluid level of CA125 in HCV cirrhotic patients (decompensated or not) with or without Hepatocellular Carcinoma (HCC). Patients and Methods: Group I: Session [CurrentTestPartID] post HCV liver cirrhosis cases; (A) 30 cases without ascites, (B) 30 cases with ascites. Group II: Session [CurrentTestPartID] HCC of post HCV liver cirrhosis cases; (C) 30 cases without ascites, (D) 30 cases with ascites. Serum and ascetic fluid level of CA-125 as well as serum AFP were assessed in all cases. Results: Serum level of CA-125 between group A&B being higher in group B (P<0.01), however between groups C&D being higher in group D (P<0.01). There was a positive correlation between serum level of CA-125 and AFP level in group A and C (P>0.05). Regarding Group B and D, there was a positive correlation between serum level of CA-125 and each of AFP level (P>0.05) and ascitic level of CA-125 (P<0.01). Concerning the ascitic level of Ca 125, being higher in group D than B (P<0.01). Only AFP had a significant diagnostic performance (P<0.01) in differentiating HCC groups from non-HCC groups. Conclusion: Elevated serum and ascetic level of CA125 in decompensated cirrhosis with or without HCC. AFP had a diagnostic performance in HCC diagnosis