Purpose: to evaluate the potential clinical value of lens culinaris agglutinin reactive alpha-fetoprotein (AFP-L3) against total AFP in the diagnosis of HCV related HCC and to evaluate its role in disease diagnosis. Subjects and methods: this study included 40 patients who were diagnosed as hepatocellular carcinoma; diagnosis was based on The BCLC staging classification, 20 patients with chronic liver disease and 20 healthy subjects as a control group. Results: showed that, there was a significant positive correlation between each of serum AFP, AFP-L3, with each of tumor size and tumor number, among HCC patients. the median value of both serum AFP-L3 and AFP-L3/AFP ratio was significantly higher in HCC patients group when compared to chronic liver disease patients and normal control individuals. Receiver operator characteristics (ROC) curves were constructed for serum AFP, AFP-L3 and AFP-L3/AFP ratio as predictors of HCC. Serum AFP-L3 had the largest area under the curve (AUC). The best cut-off point for AFP as predictor of HCC was 128ng/mL (sensitivity 75%, specificity 100%, PPV 100%, NPV 66.7% and efficacy 83.3%). The best cut off point for AFP-L3 as predictor of HCC was 23 ng/mL (sensitivity 97.5% specificity 100%, PPV 100%, NPV 95.2% and efficacy 98.3%). The best cut-off point for AFP-L3/AFP ratio was 16 % (sensitivity 97.5%, specificity 100%, PPV 100%, NPV 95.2% and efficacy 98.3%). Conclusion: In conclusion AFP-L3 is a promising marker for diagnosis of HCC especially when combined with AFP as the diagnostic sensitivity was optimum so both markers can be used in the screening of HCC.