The handling of cytotoxic drug [CDs] is currently considered to be an occupationally hazardous. Therefore, safety measures must be followed to protect health care personnel, especially nurses, who are always exposed to these drugs in the hospital setting. The aim of this study was to evaluate the effect of nurses' knowledge and beliefs concerning occupational exposure about their practice while handling CDs. The study was carried out at the Oncology Care Unit at the Main University Hospital of Alexandria University. The sample of this study consisted of all nurses [No =40] who are responsible for preparation and administration of CDs in Oncology Care Unit. Two tools were used to collect the necessary data. Tool I: A questionnaire to assess nurses' knowledge and beliefs was developed, in addition to a list of symptoms and reasons for not following preventive measures guidelines. Tool II: Consists of an observation checklist to assess nurses' practice of safety measure during preparation and administration of CDs. A gap was found between the nurses' knowledge and beliefs on one hand and their practice of safety measures during handling CDs on other. The study finding support the need to promote primary prevention by providing a safe environment for nurses by means of education, training with regards to safety measures, unit policy, written rules, and guidelines.