Background: Experience with Des-gamma Carboxy Prothrombin (DCP) is limited. Most studies on HCC biomarkers have focused on the accuracy of markers for diagnosis. Objective: To assess serum level of Des-gamma carboxy prothrombin as a biomarker for early detection of hepatocellular carcinoma post chronic active hepatitis on top of hepatitis C virus infection (HCV). Patients and Methods: This study was conducted on 60 individuals diagnosed as chronic HCV patients, and 30 healthy individuals were selected as a control group. Fifteen patients were suffering from chronic active hepatitis without complications, Fifteen patients were suffering from chronic active hepatitis with complications, Fifteen patients were of early cases of HCC on top of HCV, and Fifteen were patients of late cases of HCC on top of HCV. Des-gamma Carboxy Prothrombin were measured by ELISA. Results: There was significant increase in Des-gamma Carboxy Prothrombin (DCP) in group (II) and group (III) when compared to control group (I). However, Patients in group (III) showed higher levels of DCP when compared to group (II). Conclusion: DCP was promising in overcome AFP insufficiency in identity AFP negative HCC as DCP has a superior performance than AFP in identification of HCC from HCV-related in surveillance studies.