Introduction: Many cytotoxic drugs (CDs) are known to be teratogenic and mutagenic to humans. Nurses are the main groups that are exposed to these drugs in hospital setting. Generally, the occupational activities that pose a greatest risk of exposure are the preparation and administration of CDs, cleaning of CDs spills, and handling of patient excreta. Aim of work and Objectives: This study aims to protect nurses from CDs exposure hazards with the following objectives: 1)To determine health hazards of CDs exposures.2)To apply a health education program for improving knowledge and practice of nurses exposed to CDs.3)To evaluate the effect of health education program on improving the knowledge and practice of nurses exposed to CDs. Materials and Methods: An interventional study (health education program) carried on 50 nurses exposed to CDs in oncology units (Pre and post intervention) at Zagazig University Hospitals. All nurses were subjected to a structured questionnaire included questions about: personal and socio-demographic characteristics, occupational history, and knowledge about CDs drugs. A performance checklist was used to assess the practice of nurses. All nurses were subjected to health education program. Results: Improvement in knowledge among the studied nurses was only affected by nurses' job rank as the knowledge of supervisors improved more than the knowledge of staff nurses. The  practice of nurses was not affected by socio-demographic characteristics. It also showed that there was a statistical significant improvement of total knowledge and total performance after intervention by health education (4.0% vs. 98.0% and 4.0% vs. 56.0% respectively). Conclusion: The level of knowledge of nurses about CDs was not satisfactory; also there was a significant improvement of knowledge and practices among the studied nurses handling cytotoxic drugs after intervention.