Background High prevalence of Hepatitis C virus (HCV) in Egypt considers it as the major cause of hepatocellular carcinoma (HCC). So, several attempts have been used to predict HCC but still need more. In this regard, the predicting abilities of superoxide dismutase (SOD) and catalase (CAT) activities as well as total antioxidant capacity (TAC) were tested for estimating chronic hepatitis C (CHC)-mediated HCC. Patients and methods Blood samples from 79 patients (23 CHC and 56 HCC) were withdrawn to estimate these antioxidants and the routine analysis markers. Beside 15 healthy volunteers were included Results The medians of SOD activity and TAC values were significantly elevated in sera of HCC patients with positive correlation (P<0.0001, r=0.334) when compared with those of either CHC or healthy controls (P<0.0001). On contrary, the median of CAT activity was significantly lowered (P<0.0001) with negative correlation with SOD activity (r=-0.146, P<0.04). Stepwise logistic regression analysis of the last three markers produced a score; named "Antioxidants-diagnostic" which increased the AUCs values and their diagnostic activities (P<0.0001). By combining the three marker values with that of Age-platelet index (API) produced a score named "Antioxidants-API". Also, by combining them with that of the routine analysis values produced a score named “AAI-antioxidants". In each case the AUCs values were enhanced when compared with those of its native antioxidants (P<0.0001). Conclusion The assessment of these antioxidant activities and their combination in the last three scores can enhance their activities to more precisely predict HCC patients among CHC ones and control individuals.