Background: Facing a diagnosis of breast cancer and its treatment is often equivalent to facing death itself, which leads to the emergence of powerful emotions that often seem to get out of control. After mastectomy, many women experience serious psycho-social reactions. These reactions can adversely affect their treatment outcomes and cancer prognosis. Aim of the study:  This study aimed to evaluate the effect of psycho-social program on the women with mastectomy undergoing chemotherapy. Methods:  A quasi-experimental designs one group (pre and post-test) was used. The subjects of the study included 30 women was divided into 8 group each group include 4 women who were chosen by convenience sample. The study was conducted at department of oncology in the Nasser institute of oncology at Cairo Egypt Tools for data collection: Four tools were used for data collection, Tool (1): Structure interview questionnaire Sheet which assessing patient socio-demographic data and clinical data, Tool (2): Depression, Anxiety and Stress Scale-21 Items (DASS-21), Tool (3): Rosenberg Self-Esteem Scale, Tool (4): Ucla Loneliness Scale.  Results: The study results showed that there was high significant statistical positive correlation between woman's' depression, anxiety, stress, self-esteem and loneliness levels pre and post implementation of the psycho-social program. Conclusion:   Based on the findings of the study, it is concluded that the psycho-social program has a positive effect on the women with mastectomy undergoing chemotherapy. Recommendation: The study suggests that the necessity of providing psycho-social services for women with mastectomy and keeping it aside for medical treatment, in order to reduce the emotional stress that accompanies the disease affecting the course of treatment.