Abstract:[Objective] To investigate the clinical value of serum β-galactoside-binding soluble 3 (LGALS3) in the diagnosis of nontraumatic osteonecrosis of the femoral head (NONFH). [Methods] From April 2023 to September 2023, 84 NONFH patients were enrolled as necrosis group, while other 78 healthy subjects were selected as control group. The serum LGALS3 concentration in the two groups were detected by enzyme-linked immunosorbent assay, and related clinical data were collected, including gender, age, body mass index (BMI), smoking history, NONFH etiology, number of affected sides, visual analogue scale (VAS) for pain, Harris score, and ARCO staging. The LGALS3 concentration and its relationship with clinical parameters in the groups divided by different facots were compared and analyzed. [Results] The serum LGALS3 concentration in the necrotic group was significantly higher than that in healthy group [(9.8±7.7) ng/ml vs (4.2± 4.1) ng/ml, P<0.001]. In patients with NONFH, LGALS3 concentration was significantly higher in the bilateral affected than in the unilateral involved [(14.7±8.1) ng/ml vs (5.3±3.3) ng/ml, P<0.001], the femoral head collapsed was significantly higher than the non-collapsed [(13.5± 7.3) ng/ml vs (3.1±1.2) ng/ml, P<0.001]. Based on ARCO staging, the concentration of LGALS3 gradually increased from stage I to stage IV, with statistically significant differences among the subgroups [(2.1±1.0) ng/ml vs (4.1±1.3) ng/ml vs (11.0±5.8) ng/ml vs (16.8±8.2) ng/ml, P< 0.001]. LGALS3 concentration in NONFH patients was significantly positively correlated with VAS score (r=0.843, P<0.001), whereas was significantly negatively correlated with Harris score (r=-0.710, P<0.001), and positively correlated with ARCO stage (r=0.822, P<0.001). ROC analysis showed that the area under curve (AUC) of LGALS3 concentration predicting NONFH was of 0.769. [Conclusion] Serum LGALS3 can reflect the severity of NONFH, and may be a potential biomarker for early diagnosis of the disease.