Background: Cancer related fatigue recognizes as one of the most regularly stated and distressing side effects reported by most of cancer patients and significant has long-term effect on the quality of life. Indeed, Fatigue can affect on the patient's life including physical, psychological, social and spiritual aspects. Aim: evaluate the effect of applying fatigue nursing guidelines on oncology patient health outcome. Research design: Quasi experimental design was used in this study. Sample: A convenient sample of 94 cancer patients with a fatigue reported 4 or more on a 0 to 10 numeric screening scale. Setting: the study was conducted in oncology unit at Mansoura University and Port Said General Hospitals. Methods: The study implement the National Comprehensive Cancer Network guidelines for cancer related fatigue, Functional Assessment of Chronic Illness Therapy Fatigue Scale and Fatigue management barriers were measured at baseline, one month, and three months after intervention. Results: Participants experienced significant improvements in fatigue degrees at one-month assessment, and these improvements were continued at three-month assessment. Conclusion: The nursing fatigue guideline based on the National Comprehensive Cancer Network fatigue guideline was effective in reducing fatigue severity.