Background: Hepatocellular carcinoma (HCC) is a worldwide major health problem, with increasing prevalence and poor prognosis. As regard Egypt, HCC increased due to high prevalence of Hepatitis C virus (HCV) infection. Osteopontin (OPN) is a phosphorylated glycoprotein, which play an important role in the pathogenesis of different inflammatory and fibrotic processes. Recently, OPN has developed as a promising new biomarker for HCC. Aim: This study aimed to assess the value of OPN as a biomarker for early detection of HCC in HCV positive patients with cirrhosis. Method: This study included 60 persons, divided into 4 groups each of them included 15 persons; normal persons as a control, HCV positive patients without cirrhosis, HCV positive patients with cirrhosis, HCV positive patients with cirrhosis and complicated with HCC. For all groups, History, physical examination and radiological findings were collected. OPN and AFP levels were detected by ELISA. Results: HCC patients were more likely males with a mean age 61 years. . OPN level was significantly higher in the HCC group than other groups (P