Background: Extravasation of chemotherapy is accidental leakage of chemotherapy drugs into the subcutaneous tissue tissues surrounding the administration site. Aim of the study was to evaluate the effect of intervention guidelines for prevention and management of intravenous extravasation chemotherapy on nurses' performance. Quasi- experimental research design was used. It was carried out at Pediatric Hematology and Oncology Unit of Tanta University Hospital. A convenient sample of 20 nurses working in Pediatric Hematology and Oncology Unit and responsible for providing direct care for 50 children receiving chemotherapy. Materials and Method: Four tools were used to collect data: An assessment tool of nurses' knowledge about chemotherapy, chemotherapy administration observational checklist, extravasation scale and developed intervention guidelines. The results revealed that the total scores of knowledge for more than half of nurses were poor before the guidelines application while immediately and after one month from the guidelines application the total scores of nurses' knowledge improved and all of nurses and the majority of them obtained good scores respectively. The total score of practice for three quarter of nurses' performances were poor before the guidelines application while immediately and after one month from the guidelines application the nurses' performances improved and three quarter of nurses and more than half of them obtained good scores respectively. Conclusion: it can be concluded that there was a significant improvement in nursing staff knowledge and performance in relation to prevention and management of chemotherapy extravasation. Recommendation: In-service training program should be conducted periodically for teaching to the nurses the basic clinical skills.