As one of the mainstays of breast cancer therapy, chemotherapy inevitably induces neutropenia. In this study, we explored the role of PEG-rhG-CSF (pegylated recombinant human granulocyte colony-stimulating factor) in the emergency treatment of chemotherapy-induced grades 3-4 neutropenia. A total of 100 patients with breast cancer were randomized (1:1) into the study. Fifty patients randomized to the experimental group were treated with PEG-rhG-CSF after grades 3-4 neutropenia following the first cycle of chemotherapy, while 50 patients randomized to the control group received a daily injection of rhG-CSF (recombinant human granulocyte colony-stimulating factor). The primary endpoint was the recovery time of grades 3-4 neutropenia. Compared with patients in the control group, the mean ± SD recovery time of grades 3-4 neutropenia and febrile neutropenia (FN) was significantly shorter for patients in the experimental group (grades 3-4, P = .000; grade 4, P = .000; FN, P = .038). There is no significant difference in the incidence of FN for the two groups. In the experimental group, the duration of grades 3-4 neutropenia in patients aged <60 years and ≥60 years was 2.15 and 3.20 days, respectively (P = .037). Adverse events (AEs) of any grade were reported in 37 (75.5%) and 28 (59.6%) patients from the two groups, respectively. No grade ≥3 AEs were reported. This study supported that the PEG-rhG-CSF was more effective and convenient than rhG-CSF for treating grades 3-4 neutropenia and FN in patients with breast cancer and had manageable toxicity.