Background: Regarding to the importance of self-efficacy and its impact on health-related behaviors, chronic disease management and quality of life, and limited studies in this field, present study tried to investigated the relationship between self-efficacy and quality of life in breast cancer patients undergoing chemotherapy in the Seyed-o-shohda hospital (Isfahan/Iran). Methods: This descriptive-correlational study was done in Isfahan Seyed-o-shohada hospital in 2014. Statistical population included all women who had received chemical therapy because of their breast cancer (N=130). 100 participants were selected through Cochran formula and systematic sampling. Data gathering instruments included Sherer’s standard questionnaire of self-efficacy and W.H.O questionnaire of quality of life (WHOQOL-BREF). The data were analyzed with use of the descriptive statistics and Kolmogorov–Smirnov test, one-way ANOVA and Pearson Correlation in SPSS 18. Results: The average and Standard Deviation of both self-efficacy (11.00 ± 55.78) and quality of life (15.28 ± 75.91) were estimated on the average level. There was a direct meaningful relation between self-efficacy and quality of life efficiency. The results also showed that there is meaningful relation between self-efficacy and quality of life’s dimensions including physical health, mental health, social relations and satisfaction with the environment. Conclusion: Based on the significant positive relation found between self-efficacy and quality of life it’s recommended to hold some training courses for these patients, have a physiologist in chemotherapy department, and prepare more palliative care to raise the breast cancer patients’ self-efficacy which finally leads to a better quality of life.