Abstract:[Objective] To explore the significance of serum Bax/Bcl-2 expression in non-traumatic osteonecrosis of the femoral head (NONFH) . [Methods] A total of 75 patients with NONFH and 67 healthy subjects were included in the study from March 2021 to July 2021. The serum Bax/Bcl-2 were detected by enzyme linked immunosorbent assay (ELISA) . The data were compared between the NONFH pa- tients and normal subjects. In addition, the patients were divided into different groups according to different factors, and the Bax/Bcl-2 lev- els were compared among different groups. The correlation between the serum assays and clinical data was searched, and ROC curve analy- sis was performed on Bax/Bcl-2 and whether osteonecrosis of the femoral head happened. [Results] The NONFH patients had significantly higher serum Bax and Bax/Bcl-2 than the normal controls [(2.8±1.9) vs (1.4±0.7) , P<0.05] . Of the NONFH patients, there was no significant difference in Bax/Bcl-2 among different etiological subgroups (P>0.05) , however, the bilateral affected had significantly higher Bax/Bcl-2 than the unilateral affected (P<0.05) , the patients with femoral head collapsed had significantly higher Bax and Bax/Bcl-2 than those with- out femoral head collapsed (P<0.05) . As ARCO classification progressed, the Bax and Bax/Bcl-2 upgraded significantly (P<0.05) . In terms of correlations, the levels of Bax and Bax/Bcl-2 was positively correlated with ARCO stage and VAS score (P<0.05) , whereas negatively cor- related with Harris score (P<0.05) . Furthermore, the ROC curve analysis showed that the area under the curve (AUC) of Bax/Bcl-2 for the predication of NONFH was of 0.844. [Conclusion] The level of serum Bax/Bcl-2 is related to the severity of NONFH, and may be used as a potential index for clinical judgment of NONFH.