Objective To evaluate the efficacy and safety of TNF-α antagonists in the treatment of chronic recurrent multifocal osteomyelitis (CRMO) in children. Methods The clinical data of 6 children with CRMO admitted to the hospital from June 2021 to May 2023 were retrospectively analyzed. Results A total of 6 children (4 boys and 2 girls) with CRMO were included. All of them had the onset of bone pain. The median age of onset was 9.5 (8-10) years, and the median age of diagnosis was 11 (10-12) years. The levels of C-reactive protein, interleukin-6 and erythrocyte sedimentation rate increased in 4 cases, antinuclear antibody was positive in 3 cases, and human leukocyte antigen B27 was positive in 1 case. From the onset of the disease to the last follow-up visit, a total of 92 lesions of skeletal involvement were found in the 6 children, predominantly in the tarsus (32, 34.8%), metatarsus (14, 15.2%), femur (9, 9.8%), and tibia (9, 9.8%). All 6 children received treatment with diclofenac sodium, methotrexate and adalimumab after diagnosis. Cases 1, 2, 4 and 6 received adalimumab at a dose of 40mg each time (once every 2 weeks), while cases 3 and 5 received adalimumab at a dose of 20mg each time (once every 2 weeks). Before admission, case 1 had a history of using adalimumab. After the recurrence of the disease, the efficacy of adalimumab was poor. The medication was then adjusted to infliximab at a dose of 200mg per administration (4mg/kg each time, once a month). After treatment, the condition was significantly relieved. After regular treatment for 3 months, the bone pain symptoms disappeared in 4 of the 6 children. For case 1, the bone pain disappeared after 8 months of treatment with infliximab, and for case 4, the bone pain disappeared after 4 months of treatment with adalimumab. During the follow-up process, all the children's inflammatory indexes returned to normal, and the imaging suggested that the lesions were significantly absorbed or disappeared compared with before treatment, and no TNF-α antagonist-related adverse drug reactions were seen. Conclusions TNF-α antagonists can control inflammation and improve symptoms and imaging changes in children with CRMO. No adverse drug reactions were observed during the follow-up period.