Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and it is one of the major causes of death. HCC is now a rather common malignancy in Egypt which usually develops on top of liver cirrhosis secondary to viral infection.Aim : To determine the expression profile of two candidate biomarkers (SERPINI1, and QP-C) in the liver biopsy in patients with primary HCC and to compare their expression in patients with HCV whether they are cirrhotic or not and in normal subjects. This study was conducted on 21 patients with HCC using triphasic computerized tomography (CT) scan and histopathologicalassessment (when needed) and 24 cirrhotic patients with noevidence of HCC as well as 25 HCVnoncirrhotic and 7 healthy subjects who served as control group. We determined the level of (SERPINI1 and QP-C) for all cases together with full clinical assessment, liver biochemical profile, viral markers, conventionalultrasound (US), abdominal triphasic CT scan and guided liver biopsy for HCC cases with atypical CT pattern. we found that SERPINI1 and QP-C is highly expressed in HCC group than cirrhotic group with sensitivity and specificity within 80% and 70% respectively for SERPINI1 and sensitivity and specificity within 65% and 79% respectively for QP-C. Tissue marker SERPINI1 and QP-C is highly expressed in HCC and so their use as independent tumor marker in the diagnosis of HCC is to beconsidered