Background: Nurses are often exposed to various infections during the course of carrying out their nursing activities. Therefore nurses should have knowledge and strict adherence to infection control practice. Aim: The study aimed to assess the level of knowledge and level of practice of infection control measures among staff nurses. Methods: A descriptive correlation research design was utilized with total sample of (245) staff nurses who were working in Meniet El-Nasr Central Hospital that affiliated to Ministry of Health. Tools of data collection: Self-administered questionnaire sheet was used to assess nurses' knowledge about infection control measures and an observation checklist that was used for assessing staff nurses' practice. Results: Revealed that 85.3% of staff nurses had unsatisfactory knowledge and 71.0% of them had inadequate practice regarding infection control measures. Conclusion: The findings pointed to, the majority of the staff nurses had unsatisfactory knowledge and inadequate practice regarding infection control measures. Recommendations: Training course program is necessary to increase nurses' knowledge and practice towards nosocomial infection control measures regularly.