Background and study aim : Many studies have reported that insulin resistance raises the risk of primary hepatocellular carcinoma (HCC). Caspase-generated cytokeratin-18 (CK-18) fragments are produced during apoptosis of hepatic cells. The present study aims to evaluate the value of serum CK-18 and the impact of insulin resistance on recurrence of HCV related HCC in patients treated with radiofrequency ablation (RFA). . Patients and Methods: The present study was conducted on 60 HCV patients. Group I: 30 patients with HCC treated by RFA and group II: 30 non HCC cirrhotic patients. Insulin resistance was estimated by the homeostatic model assessment of insulin resistance (HOMA-IR) and CK-18 level was measured for all patients using ELISA. Results: HOMA-IR and CK-18 levels were significantly elevated in HCC patients when compared to non HCC cirrhotic patients. There was a significant increase in CK-18 and HOMA-IR levels in patients with local recurrence versus those with no recurrence (p<0.001). Univariate analysis revealed that HOMA-IR (p=<0.001) and CK-18 (p=<0.001) were significant predictors of recurrence of HCC. Conclusion: CK-18 and HOMA-IR are potential prognostic markers as they can predict the recurrence of HCC.