Background: Liver cirrhosis is characterized by poor life expectancy and is a leading cause of morbidity and mortality. It carries the risk of life-threatening complications, partly due to a number of co-morbidities. Purpose: to examine effect of a designed nursing intervention on knowledge and fatigue among patients with liver cirrhosis. Design: A quasi-experimental research design was carried out .It conducted in outpatient clinic in Hepatology Department, National Liver Institute, Menoufia University, Egypt. A purposive sample of 80 patients with liver cirrhosis was included. Three instruments was used, a structured interviewing questionnaire that include socio-demographic data and medical data, Knowledge Assessment Questionnaire and Fatigue impact scale (FIS). Results: There was a significant statistical improvement in knowledge score at post intervention compared to pre intervention. A highly significant improvement appeared in the fatigue categories after nursing intervention. Conclusion: Implementing of a designed nursing intervention has a significant role in improving knowledge and reducing fatigue among studied patients with liver cirrhosis. Recommendations: Providing continuous self-care education programs for liver cirrhotic patients in hepatology units to overcome symptoms and complications of the disease.