Objective: To explore the curative effect of ifosfamide combined with MVAC (methotrexate, vincristine, adriamycin and cisplatin) to treat osteosarcoma.Methods: Data from patients with osteosarcoma admitted to the Second Hospital of Nanjing and the Fourth Hospital of Hebei Medical University from February 2020 to February 2021 were selected for a retrospective analysis. They were 1:1 divided in the experimental group (EG) and the control group (CG) according to the treatment method applied. The CG was given MVAC, and the EG received MVAC and ifosfamide. Short-term efficacy, inflammatory factors levels and the incidence of adverse reactions between the two groups was assessed.Results: Overall, 120 patients were included in the study. Treatment efficiency in the EG was higher than in the CG (p < 0.05). Tumor necrosis factor-& alpha; (TNF-& alpha;),c-reactive protein (CRP) and white blood cell (WBC) levels in the EG were overtly lower. Interleukin-10 (IL-10) level was significantly higher compared to the CG (allp < 0.001). Adverse reactions incidence in the EG was lower than in the CG (p < 0.05). Conclusions: Ifosfamide and MVAC combined to treat osteosarcoma show a good safety profile, with improved inflammatory factors levels.