Aim: The aim of this study is to identify the prognostic value of serum interleukin (IL)-18 level in hepatitis C virus (HCV) -related hepatocellular carcinoma (HCC) patients. Materials and Methods: This study was conducted in Tropical Medicine department and HCC unit in Ain Shams University Hospitals. It included 35 patients with HCV associated HCC fit for radio frequency ablation and 20 healthy control subjects. Serum IL-18 level was measured for all participants at the beginning of the study. Patients were followed-up for 1 year then serum IL-18 re-measured at the end of the follow-up period. Results: Pre-intervention serum IL-18 level was significantly higher in patients than healthy control subjects and was associated with bad clinical, laboratory or radiological prognosis. Post follow-up mean value of IL-18 level was significantly lower than pre-intervention level. Conclusion: Higher pre-intervention serum IL-18 level in HCV -related HCC patients level was associated with bad prognosis either clinically, laboratory or radiologically.