Background: Hepatocellular carcinoma (HCC) is the most common primary hepatic tumor and one of the most common cancers worldwide. New serum tumor markers are required for diagnosis of HCC as alpha-fetoprotein (AFP), which is the most widely used marker, has poor diagnostic accuracy. Hepatocyte growth factor (HGF) initially identified and molecularly cloned as a potent mitogen of primary cultured hepatocytes, has multiple activities in a variety of tissues during the course of development and also in various disease states. Aim: This study was conducted to assess the diagnostic value of serum HGF as a biomarker for diagnosis HCC. Methods: This study was conducted on 30 patients with documented HCC and 30 cirrhotic patients with no evidence of HCC; as well as 25 healthy subjects who served as control group. The levels of AFP and HGF were measured for all cases together with full clinical assessment, liver biochemical profile, viral markers, ultrasound, and abdominal triphasic computerized tomography (CT) scan. Results: The mean value of serum HGF was highly significantly elevated in HCC group compared to the control group (P = 0.008), and its level was higher in HCC than cirrhotic group (795.8 ± 312.04 Vs 322.7 ± 45.2 respectively) but with insignificant difference (P = 0.92). There was significant correlation between serum HGF level and both ALT, MELD score in HCC group (P = 0.005, 0.02 respectively). At cut off level 426.1 pg/ml, HGF could diagnose HCC with 96.7% sensitivity and 98.2% specificity and AUROC was 0.99. Conclusion: Serum level of HGF could be considered useful marker for diagnosis of HCV related HCC.