Background: The burden of hepatocellular carcinoma (HCC) has been increasing in Egypt with a doubling in the incidence rate in the past 10 years. Elevated serumvascular endothelial growth factor (VEGF) have been related to poor prognosis inpatients with HCC. VEGF gene polymorphisms have been shown to be independentlyassociated with an adverse outcome in various malignancies including HCC. Background: The burden of hepatocellular carcinoma (HCC) has been increasing in Egypt with a doubling in the incidence rate in the past 10 years. Elevated serumvascular endothelial growth factor (VEGF) have been related to poor prognosis inpatients with HCC. VEGF gene polymorphisms have been shown to be independentlyassociated with an adverse outcome in various malignancies including HCC. Aim of the work: This study tries to evaluate the role of serum VEGF, +936 and 634 gene polymorphisms as non invasive biomarkers for prognosis of HCC in Egyptianpatients. Subjects and methods: Serum VEGF was measured in 26 healthy control, 13positive anti-HCV antibodies control individuals and 50 HCC patients on top of livercirrhosis using quantitative sandwich ELISA technique, both +936 and 634 gene polymorphisms were detected in the control subjects and patients using PCR-RFLPtechnique. Results: VEGF 634 G allele frequency showed a statistically significant increase in HCC, HCVand healthy controls (57%, 53.8% and 26.9%, respectively) as compared tothe protective C allele frequency which was 43%, 46.2% and 69.2% respectively(P=0.002), OR= 1.136, 95th CI(0.476-2.703). VEGF 936 T allele showed statisticallysignificant increase in HCC (52%) as compared to HCV group (19.3%), and healthy control group (7.7%) (P= 0.001), OR= 4.5, 95th CI (3.23-6.23) as compared to theprotective C allele that was (48%) in HCC, (80.7%) in HCV control group, and (92.3%)in healthy control group. VEGF 634 G/G genotype was significantly detected in large tumour size (P=0.005),PVT (P=0.047), positive anti-HCV antibodies (P=0.017) and liver cirrhosis (P=0.008),meanwhile, +936 C/T genotype was statistically significant with large tumour size(P=0.003) and portal vein thrombosis (PVT) (P=0.037). Serum VEGF level was significantly higher with 634 GG genotype and+936 CT genotype among the three studied groups (P=0.001, P=0.000) respectively and with PVT(P=0.012) and presence of positive anti- HCV antibodies in HCC group (P=0.001). A significant correlation was observed between serum VEGF and tumour size (P=0.000, r =0.573), multiple tumour masses (P=0.004), r=0.564), and AFP (P=0.000, r=0.623). Conclusion: Serum VEGF and both +936 and 634 gene polymorphisms have thepotential to be novel biomarkers for prognosis of HCC Egyptian patients.