Objective To explore the efficacy and safety of combined surgery with triamcinolone acetonide and methylprednisolone respectively in the treatment of granulomatous mastitis. Methods: A total of 92 patients with granulomatous mastitis admitted to Jiyuan People's Hospital were included in this study. They were divided into the control group (46 cases, treated with oral methylprednisolone) and the study group (46 cases, locally injected with triamcinolone acetonide) according to the treatment methods for retrospective analysis. All patients underwent surgical treatment after meeting the surgical criteria after treatment. Both groups of patients were followed up for half a year after the operation. The clinical indicators of the two groups of patients, the serum inflammatory factor indicators before and after treatment, the immune function indicators, and the occurrence of adverse reactions were compared. Results: The time for pain disappearance and the time for mass softening in the study group were shorter than those in the control group (t=18.479, 22.513, 15.705, all P<0.05). After the treatment, the levels of various serum inflammatory factor indicators in both groups decreased compared with those before the treatment, and the level in the study group was even lower (t=7.105, 3.845, 5.646, all P<0.05). After the treatment, the levels of various immune function indicators in both groups decreased compared with those before the treatment, and the level in the study group was even lower (t=8.697, 3.308, 12.361, all P<0.05). The total incidence of adverse reactions in the study group was 8.70%, which decreased compared with 23.91% in the control group (χ2=3.903, P<0.05). The patients were followed up for half a year after the operation, and no disease recurrence occurred in either group. Conclusion: Compared with oral methylprednisolone combined with surgical treatment, local injection of triamcinolone acetonide combined with surgery in the treatment of granulomatous mastitis can effectively relieve clinical symptoms, signs and pain degree, reduce inflammatory response, inhibit excessive immune response, and has higher safety.