Abstract The aims of this study was to assess knowledge and practice of nursing staff working in the GI endoscopy center, to determine the nursing intervention for patient undergoing upper GI endoscopy, then to design a teaching protocol, lastly to evaluate the effect of implementing the protocol on nurse's knowledge, practices. Subjects and methods: A quasi-experimental research design was conducted to meet the aim of the study; the sample included all convenient nursing staff working with patient undergoing upper GI endoscopy (30 nurses). This study conducted at GI endoscopy center at Assiut University Hospital. Two tools used for collecting data in the study. Tool one is a pre/post nurses' performance assessment sheet. Tool two is a designed teaching protocol. Results show a good improvement in the knowledge & practice scores after implementing protocol. A positive correlation between nurse's knowledge and practice scores after implementing protocol. Conclusion of this study illustrated that the implementing of the designed nursing protocol on nurse's knowledge and practice regarding upper GI endoscopy patients shows a significant improvement in nurses' performance's. The study recommended that continued nursing education and in-service training programs in the GI endoscopy center should be organized regularly and the nurses should use pre, post nursing teaching guidelines according to protocol for caring with patient undergoing upper GI endoscopy.