Background: hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and it is one of the major causes of death, because of its high frequency and poor prognosis. Hepatocellular carcinoma is now a common malignancy in Egypt which usually develops on top of liver cirrhosis secondary to viral infection, as hepatitis C viruses increased the risk of HCC in the Egyptian patients. Aim of the Work: was to verify the possibility of using the plasma squamous cell carcinoma antigen level as a tumor marker for hepatocellular carcinoma and to evaluate its prognostic value in management of HCC. Patients and Methods: the study included 60 subjects divided into three groups: group I was 30 patients with hepatocellular carcinomas, group II was 15 patients with liver cirrhosis and group III was 15 normal subjects serving as a control group. Results: the plasma SCCA level was significantly higher in group I patients (with HCC), than in the group II patients (cirrhosis) and control group. SCCA showed direct significant correlation with the most of laboratory data specially AST, INR, number and size of lesion. Conclusion: plasma SCCA is a sensitive and specific serum marker for the diagnosis of HCC and combination of AFP and SCCA in screening and diagnosis of HCC yielded a better sensitivity in diagnosis of HCC.