Background: Patients with depression have deficits in self-care skills and self-efficacy to help for resolve this discrepancy; it was necessary to have an intervention program to raise the level of self-efficacy and improve self-care skills among patients with depression. Aim: This study aimed to evaluate the effect of intervention program on self-care skills and self-efficacy among patients with depression. Design: This study followed a quasi-experimental research design (pre/post-test) one group. Setting: The study was carried out the inpatient wards at El-abbassia Psychiatric Mental Health Hospital and Benha Psychiatric Mental Health Hospital. Sample: This study was conducted on 40 patients with depression. Tools of data collection: The study tools divided into three tools, (I) Structured Interview questionnaire sheet, (II) Self-care scale, (III) Self-efficacy scale. Results: There was a marked improvement in total self-care skills and self-efficacy post implementation of intervention program with a highly statistically significant difference between pre and post implementation of intervention program among the studied patients. Also, there was a highly statistically significant positive correlation between total patients' self-care skills and total selfefficacy at pre and post-implementation of the program. Conclusion: Intervention program have a marked improvement in total self-care skills and self-efficacy among patients with depression. Recommendations: Continuous in-service training programs for nurses about enhancing self-care skills and self-efficacy skills are need to be implemented to provide basic necessary skills among patients with depression .