Background & Aims: Health related quality of life is one of the important concepts that nowadays is considered along with other quantitative criteria like life expectancy and survival in health service systems, but its significance is more obvious in degenerative diseases and long term treatments such as cancers. In this study we compared health related quality of life in breast cancer patients undergoing either Docetaxel – Adriamicine - Cyclophosphamide (TAC) or 5-FU- Adriamicine – Cyclophosphamide (FAC) regimens. Method: This study was conducted in a double blind cohort design on 100 patients with positive - node breast cancer treated by TAC or FAC regimens. The international standard questionnaire (EORTC QLQC30) was used to evaluate health related quality of life at the start and end points of chemotherapy period. Data were analyzed by independent t-test at the significant level of 0.05. Results:Results showed the same scores of quality of life at the first session of chemotherapy in both groups and in 4- month follow up, at the end of chemotherapy, mean score of quality of life in both groups decreased but it reduced more in TAC group. Conclusion: Chemotherapy regimens can decrease patients` quality of life greatly. So reinforcing the relationship between patients and their families, society and treatment team in addition with using supportive methods and counseling groups can maintain the level of patients` quality of life greatly.