Objectives The aims of the study were to determine serum levels of interleukin-22 (IL-22) in patients with liver cirrhosis in Menoufia University Hospitals and to detect its relation with the degree of liver cirrhosis and determine the serum level of IL-22 in relation to morbidity of patients with advanced liver cirrhosis. Background IL-22 was recently identified as a crucial parameter of pathology in experimental liver damage. Assuming that IL-22 has hepatoprotective properties in liver diseases, IL-22 may be a relevant factor for progression of liver cirrhosis. Patients and methods The study was conducted on 40 liver cirrhotic patients and 20 age-matched and sex-matched healthy individuals. All patients were subjected to history taking, complete medical examination, and thorough laboratory and radiological investigations. Serum IL-22 levels were measured by means of the ELISA technique. Results Hepatitis C virus was the major cause of liver cirrhosis in our studied group (72.5%). The majority of patients presented with liver cirrhosis-related complications at the time of inclusion into the study. Liver cirrhotic patients had significant elevation in serum levels of IL-22 when compared with healthy people (P Conclusion Serum IL-22 is significantly elevated in liver cirrhotic patients and it may be relevant for the prognosis of advanced liver cirrhosis.