This study was conducted on 25 healthy controls, 25 cirrhotic patients and 30 patients with HCC. All patients had been diagnosed with HCVassociated chronic liver disease.Methods: SerumPIVKA-II andAFPwere measured by enzyme linked immunosorbent assay (ELISA), while telomerase activity in peripheral blood was estimated by polymerase chain reaction- enzyme- linked immunosorbent assay (PCR- ELISA method). Results: Mean telomerase activity, PIVKA-II and AFP levels were significantly higher in HCC patients as compared to both cirrhotic patients and controls, also a significant elevation in cirrhotic patients were found as compared to controls. Positive correlation was found between telomerase activity and size of hepatic focal lesions. Also, a positive correlation was found between both telomerase activity and PIVIKA-II and between the pathological grades of HCC. In HCC the sensitivity/ specificity (88.2/79.6) of telomerase activity was much higher than both PIVIKA-II (80.5/69.3) andAFP (72.6/61.5). Conclusion: The usefulness of telomerase activity assay in HCC diagnosis and itÂs superiority to other tumor marker were recorded. Therefore, telomerase activity is a novel, available detector and prognostic marker for HCC diagnosis.