Objective To compare the efficacy and safety between hypofractionated radiotherapy (HyRt) and conventional radiotherapy after breast-conserving surgery. Methods This study was a single-center, prospective, randomized controlled study. Eighty-three patients with pTis-T₂N₀M₀ breast cancer admitted to Tangshan People's Hospital from May 2017 to May 2019 were included. The patients received breast-conserving surgery + sentinel lymph node biopsy (SLNB). After surgery, they were treated with intensity modulated radiation therapy (IMRT). According to random table method, patients were divided into HyRt group (n=41) and conventional radiotherapy group (n=42). The dose of organs at risk, treatment efficacy, treatment failure modes, and radiotherapy related adverse reactions were analyzed in the two groups. The radiotherapy-related adverse reactions were evaluated according to NCI CTC AE Version 3.0, including radiation dermatitis, radiation pneumonia, breast/skin fibrosis, pulmonary fibrosis, etc. Results Eighty-three patients with breast cancer were included, with a median age of 44 (26-67) years. There was no statistically significant difference in clinical parameters such as age (P=0.443), TNM stage (P=0.335), molecular typing (P=0.333), degree of differentiation (P=0.617), and pathological type (P=0.127) between the two groups of patients. Compared with conventional radiotherapy group, the V5 (25.6% vs. 33.8%, P=0.015), V20 (13.3% vs. 17.2%, P=0.042), and the mean radiation dose (MLD; 7.4 Gy vs. 10.4 Gy, P=0.020) of the affected lung of HyRt group significantly decreased. Only 3 patients in this study experienced distant metastasis, and no regional lymph node metastasis or local recurrence was observed. There was no significant difference in PFS rate at 2 years between HyRt group and conventional radiotherapy group (94.4% vs. 85.2%, P=0.818). Compared with conventional radiotherapy group, the incidence of ≥ grade Ⅱ irradiation dermatitis in HyRt group was significantly reduced (2.4% vs. 21.4%, P=0.015). There was no difference in the incidence of grade Ⅰ breast/skin fibrosis (19.5% vs. 14.3%, P=0.570) between the two groups, and no grade Ⅲ radiotherapy-related side effects were observed in the two groups. Conclusions Compared with conventional radiotherapy with simultaneously integrated boosting-intensity modulated radiotherapy, the patients who received HyRt after breast-conserving surgery for early-stage breast cancer have good tolerance and low incidence of adverse reactions. HyRt can be used as the first option of radiation therapy.