Background: Increased exposure to ionizing radiation exposes nurses and patients to health risks. Adhering to safety precautions can help lower the risk of health-related incidents. Aim: The aim of this study was to evaluate the effect of radiotherapy safety protocol on protective measures practices for oncology nurses. Study design:  The current study employed a quasi-experimental research approach, specifically a one-group pretest-posttest design. Setting: This study was conducted at Oncology and Nuclear Medicine at Mansoura Hospital and Damietta Cancer Institute. Subjects:  A convenient sample of available nurses working in previously mentioned settings (60) nurses. Tool: Two tools used for data collection: the Workplace Observation Checklist and the Nurses' Observational Checklist. Results: Most areas for improvement were wearing protective measures such as Thyroid shield, personnel monitoring devices ranged from (20,0%), (10,0%) respectively to (90,0%) and reporting of hazards that may occur from radiation such as cancer and blood changes ranged from (48.3%), (60,0%) respectively to (100%) post protocol implementation. Conclusion: Nurses' levels of protective measures practices for radiotherapy had improved after the implementation of the safety protocol. Recommendations: Training sessions are required to improve staff safety practices and ensure good performance.