Blood transfusion generally refers to the therapeutic use of blood and components. There are several risks associated with blood transfusion. According to WHO (2009) more than 81 million units of blood are collected globally every year. Through 2010, units of blood for internal medicine and blood disease unit are more than 3168 units. The nurse plays a critical role in caring for patients undergoing blood transfusion. The aim of the study was 3 folds: the first is to assess the patient undergoing blood transfusion of physical and psychological needs; the second is to assess nurses' knowledge and practice before and after implementing the protocol and the third is to design nursing intervention protocol. Hypotheses: Hypotheses were formulated: (1) The post mean knowledge score of nurses who would be exposed to design nursing intervention protocol would be higher than their pre mean knowledge scores. (2)The post mean practice scores of nurses who will be exposed to design nursing intervention protocol will be higher than their pre mean practice scores.(3) A positive relationship would be exist between knowledge and practice score obtained by nurses receiving the designed nursing intervention protocol. (4) The incidence of complications of blood transfusion after protocol implementation would be lesser than that developed pre protocol. Research design: A quasi-experimental research design was utilized in this study on a convenient sample of 55 nurses and 30 patients control group and 30 study group patients. The study will be conducted in the general medical departments (B and C) and blood diseases unit at Assiut University Hospital. Tools utilize for data collection were a) pre and post nurses' intervention interview sheet. b) Construction of designed nursing intervention protocol. c) Patients' complications assessment sheet. Results: The first and the second hypotheses were supported as a good improvement in the mean knowledge & practice scores were found after the implementing of nursing intervention protocol. The third hypothesis was supported as was not able to extract the statistical significance of the relationship between knowledge and nursing practices before and after the study but extract a positive correlation by figure. The fourth hypothesis was supported as the complications of blood transfusion after protocol implementation were lesser than that developed pre protocol. Conclusion: Improved nurses' knowledge and practice can favorable affect the incidence of complications for patient undergoing blood transfusion. Recommendation: Nurses are in need for in-service training programs and refreshing courses to improve their knowledge which will reflect on their practice while providing care to patients.