Background: Hepatic encephalopathy (HE) is a decline in brain function that occurs as a result of severe liver disease .The nurses plays a vital role in improving hepatic encephalopathy patient prognosis through providing quality of care to those patients. So, it is important to understand nurses' perception and to comprehend the factors influence their care. Aim of the study was to assess factors affecting nurses' performance regarding nursing management of patient with Hepatic encephalopathy. Subjects and methods: Research design: A descriptive study was utilized to meet the aim of this study. Settings: Data were collected from Medicine intensive care units and Endemic ICU at Zagazig University Hospitals. Subjects: A convenience sample of all available nurses who working in the above mentioned setting. Tools of data collection: Three tools were used, An Interview Questionnaire, Observational Checklist and Factors Affecting Nurses' Performance Questionnaire. Results: This study revealed that only 14.0% and 24.0% of the studied nurses had satisfactory knowledge and practice level respectively regarding management of patient with HE, as well as 90.0% of the studied nurses reported that there performance was affected by nurse, patient, and work related factors.  Conclusion: This study concluded that the highest percentage of the studied nurses has unsatisfactory total knowledge and practice level regarding management of patient with HE. Also, the most of the studied nurses' performance was affected by nurse, patient, and work related factors. Recommendations: The nurses working in the study settings is need for more addressing the factors affecting performance by hospital administration in order to improve their performance regarding management of patients with HE.