Oxygen is life essential so it is important for nurses who are responsible for oxygen administration to be familiar with its Indications and potential hazards. Aim: To investigate the effect of educational program about oxygen therapy on the nurses' knowledge and nurses' practice. Design: A Quasi experimental research design was used. Setting: The study was carried in pediatric emergency unit at Assuit pediatric University Hospital. Subjects: All available nurses in the emergency department who were (50) nurses. Tools: Two tools were utilized, Tool (1): Structure Interview Questionnaire to assess nurses' knowledge, Tool (2): Nurses' practice observational check list to assess performance. Method: preparatory, implementation and evaluation phases were used to implement study. Results: The total nurses' knowledge mean score improved from (9.080±4.818) before educational program to (19.840±.421) after its implementation, and total nurses' performance mean score improved from (63.0400 ± 7.94101) before implementation of educational program to (97.9200± .39590) after its implementation. There was good improvement with highly significant difference (p < 0.001) related to knowledge and practice of educational program. Conclusion: Majority of nurses had a satisfactory level of knowledge and practice toward oxygen therapy after applying educational program. Recommendations: Provide in-service education and training program for nurses regarding oxygen therapy