within the body. Several studies have shown that exposure to chemotherapy can cause toxic effects on reproduction system and carcinogenic effects on health-care worker especially nurse. So nurses should know how to protect themselves, their patients, and their work environment against toxic effect of chemotherapy. Aim of this study was carried out to examine the effect of chemotherapy safety protocol for oncology nurses on their protective measure practices. Research questions are: What is the effect of chemotherapy safety protocol for oncology nurses on knowledge about protective measures practice for chemotherapy handling and administration? What is the effect of chemotherapy safety protocol for oncology nurses on their protective measures practice? Design: A quasi- experimental research design was utilized. Setting: This study was conducted in the medical department at Benha University Hospital and National Cancer Institute at Cairo University. Sample of this study composed of 45 nurse who are dealing with chemotherapy drugs (10) nurses from Benha University Hospital and (35) nurses from National Cancer Institute at Cairo University. Two data collection tools were used: First tool: Assessment questionnaire sheet. Second tool: Observational checklist for nursing practice. Results of the study showed that statistical significant improvement in to nurse's knowledge and practice after implementing chemotherapy safety protocol. Conclusion: there is a positive effect of chemotherapy safety protocol on nurse's knowledge and practice about chemotherapy. Recommendation: chemotherapy safety protocol should be revised, updated, and available in oncology unit in both Arabic and English language.