Background: Hepatocellular carcinoma (HCC) is a global health problem. It is the second most common cause of cancer-related mortality and the sixth most common cause of cancer worldwide, HCC development risk factors include chronic viral hepatitis, alcoholic and non-alcoholic fatty liver disorders and other forms of chronic hepatitis inflammatory illnesses ,The aim: to study the clinical usefulness of serum Neuropilin 1(NRP 1) as a diagnostic marker for HCC. Methods: This cross-sectional study was conducted on 90 individuals divided into three groups: Group I: Thirty patients with HCC, Group II: Thirty patients with liver cirrhosis(LC), Group III: Thirty apparently healthy subjects. All patients were subjected to full medical history taking, thorough clinical examination and determination of the serum level of NRP 1. Results; NRP1 level was significantly higher in HCC when compared to LC group. Also, NRP 1 level was significantly higher in HCC and LC groups when compared to control group. ROC curve of serum NRP1 showed sensitivity was 93.3%, specificity 80%, PPV of 82.4% and NPV of 92.3% with AUC of 0.842 at cutoff value of 4030 pg/ml. Conclusion: NRP-1 may represent a potential diagnostic marker for HCC