Background :Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called medical oncology. Chemotherapy is a category of cancer treatment that uses one or more anti-cancer drugs (Chemotherapeutic agents) as part of a standardized chemotherapy regimen. The goal of chemotherapy is to stop or slow the growth of cancer cells. The handling and administration of cytotoxic drugs are hazardous potentially to the health care professionals involved in their preparation and administration, and to the patients receiving them .Aim of the study: Assess nurses' performance regarding chemotherapy administration in the clinic through: Assess the nurses 'level of knowledge regarding chemotherapy administration in the clinic, assess the nurses 'level of practice regarding chemotherapy administration in the clinic and assess the nurses' level of attitude regarding chemotherapy administration in the clinic. Research design: A descriptive exploratory research design was utilized. Setting: The study was carried out in chemotherapy clinic at El-Fayoum University Hospital. Study subjects: A Purposive sample of (30) nurses who works in chemotherapy clinic included in the study. Data collection tools: Data were obtained through demographic data tool, nurses' knowledge questionnaire, nurses' observational checklist and nurses' attitude questionnaire. Results: More than two-thirds (66.7%) of the studied nurses had unsatisfactory level of knowledge and majority (83.3%) of studied nurses had unsatisfactory level of practice regarding chemotherapy administration. Approximately three quarters (73.3%) of the studied nurses had negative attitude regarding chemotherapy administration. There were statistically significant relations between the nurses' level of knowledge, practice and attitude regarding chemotherapy administration and their demographic characteristics as age .Recommendations: Designing in-service training and educational program to improve nurses' knowledge, practice and attitude regarding chemotherapy administration.