Objective To explore the application effect of different doses of Prednisone in the treatment of granulomatous mastitis (GLM). Methods From January 2015 to January 2020, 100 patients with GLM admitted to the Department of Galactophore of Huizhou Second Maternity and Child Health Hospital were selected as the research objects, and they were divided into the experimental group (n=50) and the control group (n=50) by random number table method. The experimental group was treated with Prednisone with an initial dose of 0.4 mg/(kg·d) and decreasing with the course of treatment (the dose decreased by 2.5 mg/d per week after 5 weeks of treatment), and the control group was treated with Prednisone with an initial dose of 0.75 mg/(kg·d) and decreasing with the course of treatment (the dose decreased by 5 mg/d per week after 5 weeks of treatment). Both groups of patients were treated with debridement within 6 to 8 weeks of treatment. The effect of drug treatment and the incidence of adverse reactions, surgery-related indicators and followup related indicators were compared between the two groups. Results There was no significant difference in the effective rate of drug treatment between the two groups (P＞0.05). The incidence rates of stomach discomfort, menstrual disorders, elevated blood sugar, and insomnia in the experimental group were lower than those in the control group, the differences were statistically significant (P＜0.05). There was no significant difference in the incidence of acne and weight gain between the two groups (P＞0.05). There was no significant difference in the preoperative medication time,intraoperative gland removal amount and recovery time after treatment between the two groups (P＞0.05). There were no statistically significant differences in the total incidence of postoperative complications and the recurrence rate of 1 year follow-up between the two groups (P>0.05). Conclusion There is no difference in the drug efficacy of different doses of prednisone in the treatment of granulomatous mastitis, and it has no effect on the follow-up surgical treatment and recurrence rate. However, low-dose Prednisone in the treatment of granulomatous mastitis can effectively reduce the adverse drug reactions of patients, which is worthy of further study.