Background: Hepatocellular carcinoma (HCC) is a worldwide health problem. The aim to evaluate diagnostic and prognostic role of serum Interleukin 6 (IL6) in Egyptian patients with chronic hepatitis C related Hepatocellular carcinoma (HCC). Methods: This study was conducted on 80 Egyptian participants; 35 patients diagnosed as LC (group 1), 35 patients diagnosed as HCC (group 2), and10 apparently healthy individuals (group 3). All patients included in the study, were subjected to full history taking, thorough clinical examination, routine laboratory and radiological investigations. Additionally, quantitative measurement of serum IL-6 and AFP levels using an ELISA were done for all patients and controls. Results: HCC was presented more in males (51.4%) than females (48.6%) with a mean age of 61.89 ±8.22 years. AFP and IL-6 levels were significantly higher in HCC group (group 2) than in liver cirrhosis group (group 1). IL6 at a cutoff point of (45.65pg/ml), showed a sensitivity of 85.7%, a specificity of 82.9%, PPV of 83.3, NPV of 85.3 and AUC=0.858, Comparing AUCs, revealed that combined (AFP+IL6) was significantly better than each marker alone. Serum IL-6 level was higher in patients with Child class B than child class A patients. Conclusion: Serum level of IL-6 can represent a potential beneficial biomarker for diagnosis of hepatocellular carcinoma with good sensitivity especially if combined with AFP but with low specificity and may have a limited role in prognosis of hepatocellular carcinoma.