Spontaneous bacterial peritonitis (SBP) is a severe complication of cirrhosis that requires prompt diagnosis and treatment. Interleukin -17 (IL-17) has been suggested as a potential biomarker for SBP, but its diagnostic value in cirrhotic patients remains uncertain. Objectives The study aims to determine the diagnostic value of serum and ascetic IL-17 in SBP detection in Egyptian patients with hepatitis C virus (HCV)- related liver cirrhosis. Patients and methods This case-control study enrolled 60 patients with HCV-related liver cirrhosis complicated by ascites, who were divided into two groups based on the presence or absence of SBP. The study was conducted at the Gastroenterology and Hepatology Department of the Internal Medicine Department at Menoufia University Hospitals and Shebin El-Kom Teaching Hospital between May 2021 and July 2022. Ascitic fluid analysis and measurement of serum and ascitic IL-17 levels using ELISA kits were performed at baseline for both groups. After treatment, serum and ascitic IL-17 levels were measured again in the diseased group. Results Serum IL-17 exhibited excellent diagnostic performance with an AUC of 0.934, and the best cut-off criterion of > 89 Pg/mL was able to discriminate between patients with SBP and the non-SBP group with a sensitivity of 91.54% and specificity of 96.45%. Similarly, ascitic IL-17 demonstrated excellent diagnostic performance with an AUC of 0.876, and the best cut-off criterion of > 160 pg/mL was able to distinguish patients with SBP from the non-SBP group with a sensitivity of 94.85% and specificity of 95.69%. Moreover, a significant direct correlation was observed between ascitic IL-17 and AST (R=0.263, P=0.003), platelet count (R=0.256, P=0.001), ALT (R=0.627, P< 0.001), bilirubin (R=0.418, P< 0.001), INR (R=0.845, P <0.001), blood urea nitrogen (R=0.257, P=0.001), and creatinine (R=0.294, P< 0.001). Conclusions Serum and ascitic IL-17 had excellent diagnostic performance to differentiate SBP from the non-SBP group and in monitoring therapeutic response.