Background: Schizophrenia is a severe psychiatric condition with specific characteristics that may constitute some obstacles for the therapeutic relationship. Aim of the study was to investigate the effect of psycho-educational program to improve knowledge and performance for nurses working with schizophrenic patients. Research design: A quasi-experimental research design was used to conduct this study. Setting: This study was conducted at Psychiatric and Mental Health Hospital in Benha city, Qalubia Governorate, Egypt Sample: A convenient sample technique was used to select 80 nurses. Tools of data collection: Three tools were used in this study; I- Structured interview questionnaire which included demographic data and professional characteristics of the studied nurses, II: Knowledge questionnaire and III: Management of schizophrenic patients' checklist. Results: The majority of nurses had unsatisfactory level of total performance towards schizophrenia before program implementation. While after program implementation, three-quarters of nurses had satisfactory level of total performance towards schizophrenia. Conclusion: There was a marked improvement in nurses' knowledge and performance with schizophrenic patients care post implementation of psycho-educational program with highly statistically significant difference between pre and post implementation of psycho-educational program. Recommendation: Designed educational program for nurses in psychiatric and mental health hospital; it would provide a framework for nurses' role for schizophrenicpatient care.