Background: Extravasation of chemotherapy is leakage of chemotherapy drugs into the subcutaneous tissues surrounding the administration site. Aim of the study: This study aimed to assess the effect of nursing care protocol on nurses' performance during drug extravasation among children. Research Design: A quasi experimental design (pre and posttest) was used to achieve the aim of the study. Setting: The study was conducted at the Pediatric Oncology Unit in Specialized Pediatric Hospital at Benha City. Subjects: a- A convenient sample of all available nurses (n=30) who working in the previously mentioned study setting was included during period of data collection. b- A purposive sample of available children (n=50). Tools of data collection: Three tools utilized for collection data. I: A Structured Interviewing sheet, II: Chemotherapy Administration Observational Checklists to assess nurses' practices before, during and after administration of chemotherapeutic agents for children,and III: Infiltration and extravasation scale to assess signs of infiltration and extravasation of chemotherapeutic agents. Results: There were statistically significant differences in improvement nurses' knowledge and practice regarding nursing care protocol before and after program and after three months. Conclusion: There was a significant improvement on nursing staff knowledge, performance regarding to administration of intravenous chemotherapeutic agents, prevention and management of chemotherapy extravasation and significant reduction in extravasation occurrence in studied children. Recommendation: All nurses who administer chemotherapeutic agents should complete regular periodic in services training programs to keep them up to date regarding to safe and efficient administration of chemotherapeutic agents.