Background: Cancer-related pain is one of the greatest scared consequences of cancer and its treatment. Also, cancer patients having recurrent interaction with a variety of health providers, their pain is commonly uncontrolled. Cancer-related pain identified as vital symptoms that influence on the quality of life among cancer patients. Aim: The aim of this study is to evaluate the effect of pain nursing intervention guidelines on oncology patients' health outcome.Research design: Quasi experimental design was used in this study.  Sample: A purposive sample of 94 cancer patients with a pain 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 Saied General Hospitals. Methods: The study implement the National Comprehensive Cancer Network guidelines for cancer related pain, brief pain inventory and Pain management barriers were measured at baseline, one month, and three months after applying the intervention guidelines. Results: Participants experienced significant improvements in pain degrees at one-month assessment, and these improvements were continued at three-months assessment. Conclusion: The nursing intervention practice based on the National Comprehensive Cancer Network fatigue guideline was effective in reducing pain severity. Recommendation: Pain should be assessed at least twice per day for cancer patient. Also, the patients need to receive educational materials for pain management and to reduce the barriers