The aims of this study were to analyze the acute and advanced responses of different hypofractionated radiation therapies (HFRT) after modified radical mastectomy for breast cancer (MRM-BC). A total of 162 patients were included into this prospective clinical Stage I-II study from October 2010 to May 2015, including 77 cases (group 42.5 Gy) and 85 cases (group 36.5 Gy). The acute and advanced side effects were analyzed according to static intensity modulation plan and Radiation Therapy Oncology Group (RTOG) classification criteria. There was no significant difference in the white blood cell reactions, acute skin reactions, and acute pharyngeal - esophageal reactions between group 42.5 Gy and 36.5 Gy, and no late complication was observed during follow-up. The median follow-up time of group 42.5Gy was 36 months and that of group 36.5 Gy was 12 months. There was no statistical significance in the local recurrencefree survival rate, disease-free survival rate, and distant metastasis rate between the two groups. There was no local recurrence or death in both groups (with the radiation field), and the local recurrence-free survival and overall survival rates of the two groups were both 100%. The incidence of acute adverse reactions and short-term efficacies of the two post-MRM-BC HFRT (42.5 Gy/16 F and 36.5 Gy/10 F) were similar, but the advanced adverse reactions and efficacies still need further observation.