Abstract:[Objective] To investigate the clinical value of serum homocysteine (Hcy) detecting in the early diagnosis of nontraumatic necrosis of the femoral head (NONFH). [Methods] From January 2023 to October 2023, 73 patients with NONFH and 68 healthy subjects who underwent routine physical examination during the same period were included in this study. Serum Hcy levels were determined by enzymelinked immunosorbent assay (ELISA). The difference of Hcy level between patients and normal controls, as well as groups stratified by clinical indicators in the patients was compared, and the correlation between Hcy level and relevant clinical data was analyzed, and the value of Hcy level to determine whether NONFH was conducted by receiver operator characteristic curve (ROC). [Results] The serum Hcy level in NONFH patients was significantly higher than that in normal controls [(36.3±11.8) nmol/ml vs (19.2±13.7) nmol/ml, P<0.001]. In terms of stratified comparison of 73 patients, the Hcy in the bilateral affected was significantly higher than that in the unilateral involved [(44.2±5.2) nmol/ml vs (29.4±11.7) nmol/ml, P<0.001], while the Hcy in the femoral head collapse was significantly higher than that in the non-collapsed [(43.7±4.5) nmol/ml vs (24.4±10.1) nmol/ml, P<0.001]. With the upgrade of ARCO classification, the serum Hcy level increased significantly, which was of statistically significant differences among different stages [I/II/III/IV, (15.1±2.4) nmol/ml vs (29.8±9.2) nmol/ml vs (42.1±4.4) nmol/ml vs (46.2±3.5) nmol/ml, P<0.001]. In term of correlation analysis, the serum Hcy level was of significantly positive correlation with VAS score (r=0.747, P<0.001) and ARCO staging (r=0.791, P<0.001), whereas significantly negative correlation with Harris score (r=-0.706, P<0.001). As result of ROC analysis, the sensitivity and specificity of serum Hcy level for predicting NONFH was of 67.1%, and 85.3%, with area under curve (AUC) of 0.818. [Conclusion] Serum Hcy level in NONFH is significantly elevated and positively correlated with disease severity, suggesting that Hcy maybe a potential diagnostic marker for NONFH.