Objective To explore the changes of dynamic levels and clinical significance of serum tumor necrosis factor (TNFɑ), interleukin-1 (IL-1) and bone morphogenetic protein2 (BMP-2) in patients with chronic osteomyelitis (COM). Methods One hundred patients with COM admitted to Sichuan Orthopedic Hospital were selected as study group, and 35 healthy subjects for physical examination at the same time were selected as control group. The COMrelated laboratory results and levels of serum TNFɑ, IL-1 and BMP-2 were detected and compared between the two groups. The levels of TNFɑ, IL-1 and BMP-2 were analyzed among patients with different prognostic efficacy, and Spearman or Pearson correlation analysis was used to analyze the correlation between TNFɑ, IL-1 and BMP-2 and COMrelated laboratory results ［the number of positive cases of staphylococcus aureus (SAU), erythrocyte sedimentation rate (ESR) and Creactive protein (CRP)］, and receiver operating characteristic curve (ROC) was used to analyze the diagnostic value on COM. Results The number of SAU positive cases in study group was significantly higher than that in control group (P＜0.05). The levels of ESR, CRP and serum TNFɑ and IL-1 in study group were significantly higher than those in control group (P＜0.05), while the BMP2 level was significantly lower than that in control group (P＜0.05). The serum TNFɑ and IL1 levels in good prognosis group after surgery were significantly lower than those in poor prognosis group (P＜0.05), while the BMP2 level was significantly higher than that in poor prognosis group (P＜0.05). Correlation analysis showed that serum TNFɑ and IL1 levels were significantly positively correlated with the number of SAU positive cases, ESR and CRP in COM patients, and BMP2 was significantly negatively correlated with the number of SAU positive cases, ESR and CRP in COM patients. The AUC values of serum TNFɑ, IL-[1 and BMP-2 were 0.860 (5% CI: 0.7790.941), 0769 (95% CI: 0.6700.868) and 0.881 (95% CI: 0.8210.941) respectively in the diagnosis of COM, and the AUC value with 0973 (95% CI: 09510996) and specificity with 971% of the three combined diagnosis were significantly higher than those of the single detection of above indicators (P＜0.05). Conclusion The levels of serum TNFɑ and IL-1 in patients with good COM prognosis are significantly decreased, while the level of BMP-2is significantly increased. The changes of dynamic levels of serum TNFɑ, IL-1 and BMP-2 were related to the prognosis of patients. The three combined detection can improve the specificity of COM diagnosis, and they be used as biomarkers for assisting COM.