Background: Patients with HCV face numerous emotional and psychological stressors that have a significant effect on their well beings and their quality of life. This study aimed to evaluate the effect of psycho educational program on psychological stress and quality of life among patients with Hepatitis C Virus. A quasi experimental design was utilized to achieve the aim of the study. The study was conducted in hepatic unit and medical units at Benha University Hospital, which is affiliated to the Ministry of High Education. A purposive sample of (40) patients with HCV (22 female and 18 male) was selected from the above mentioned settings. The study tools divided into three tools. Tool (I): Structured Interview Questionnaire to assess socio-demographic and clinical characteristics. Tool (II): Stress Scale and Tool (III): Quality of life scale. Results: Findings indicated that there were highly statistically significant reduction in the severity of total stress and highly statistically significant improvement in the level of total quality of life post program implementation than before. Also, there was a highly statistically significant negative correlation between total stress and total quality of life scores of studied HCV patients' pre and post program implementation. Conclusion: The psycho educational nursing program had a positive effect on the psychological stress and quality of life among studied patients with hepatitis C virus. The study recommended that generalization of psycho-educational program for all patients with hepatitis C virus in all hospitals to alleviate their psychological stress and improve their quality of life