Background: Hepatorenal syndrome (HRS) may result from decreased renal perfusion in advanced liver cirrhosis patients. Copeptin is co-secreted with the arginine vasopressin (AVP) and is increased in patients with decompensated liver cirrhosis, however, limited studies associated Copeptin with HRS. Objective: This study aimed to evaluate serum Copeptin as a predictor of HRS in advanced liver cirrhosis patients. Patients and Methods: A case-control study had been carried out on a total of 40 subjects divided into; Group 1: 20 decompensated cirrhotic patients with HRS, Group 2: 10 decompensated cirrhotic patients with normal kidney function, and Group 3: 10 healthy controls. The following had been made; history taking, clinical examination, laboratory investigations: complete blood picture, liver function tests, coagulation profile, serum sodium, and creatinine. Serum Copeptin was measured using an enzyme-linked immunosorbent assay (ELISA). Results: Serum Copeptin levels; mean ±SD in pmol/L were significantly increased in group 1 (HRS) (7.3±1.11) compared to group 2 (3.6±0.99) and group 3 (2.3±0.31) (P˂0.001). Serum Copeptin levels positively correlated with serum creatinine, prothrombin time, total bilirubin (P˂0.05), and negatively correlated with serum albumin (P˂0.05), and sodium (P˂0.001), with no correlation with other parameters. The receiver operating characteristic (ROC) curve for serum Copeptin validity as a predictor of HRS in advanced liver cirrhosis patients, at a cutoff of 3.99 pmol/L showed 95.1% sensitivity, 70.2% specificity, and 85.1% accuracy. Conclusion:Serum Copeptin may predict HRS in advanced liver cirrhosis with high sensitivity and specificity.