Background: The principles and responsibilities associated with nurse navigation align closely with the fundamentals of total quality management (TQM) in healthcare, which aims to improve quality, continuous improvement, safety, and patient satisfaction. Aim: Assess nurses' knowledge level about nurse navigation principles and responsibilities and its relation to TQM at Main Assiut University Hospital. Study design: Descriptive correlational design was used. Setting: Main Assiut University Hospital. Subjects: A convenience sample of all nurses working at Medical departments at Main Assiut University Hospital (n =41 nurses). Tools: Two tools were used to collect data namely, a structured questionnaire that consists of two parts includes personal data and principles and responsibilities of nurse navigation assessment scale. The second tool is TQM knowledge questionnaire. Results: The majority of nurses had low level of knowledge about nurse navigation (principles and responsibilities) and TQM. Conclusion: A statistically significant positive correlation exists between principles and responsibilities of nurse navigation and TQM. Recommendations: Develop and implement targeted educational programs for nurses that focus on the practical principles of navigation and responsibilities of nurse navigator and how it aligns with TQM.