Abstract: Objective To investigate the diagnostic value Tamm-Horsfall protein (THP) and osteopontin (OPN) in serum and24-hour urine for urolithiasis.Methods A total of 10l1 patients with urolithiasis who underwent flexible ureteroscopy lithotripsy at theUrology Department of Civil Aviation Cenenal Hospital from April 2020 to March 2023 were included as the stone group, and 50 healthyindlividuals were enrolled as the contml group. The samples of serum and 24-hour urine samples were collected from both the groups,and the levels of THP and OPN were measured using enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis wasperformed to evaluate the association between each biomarker and urolithiasis , and receiver operating characteristic(ROC) curves wereplotted to assess their diagnostic value.Results The stone group showe significantly lower'THP levels ( 20.13[ 13.12,26.03]mg/d)and OPN levels (51.24[36.72，101.37] u.g/d) in 24-hour urime, and THP levels ( 182.01[ 160.91,209.20] ng/mL) and OPN lev-els ( 18.76[ 15.72,22.48] ng/mL) in serum compared to the control group (all the P<0.001 ). Binary Logistic regression analysis r-vealed that'THIP(OR=0.736，95%Cl; 0.606-0.895), OPN (OR=0.975，95%CI : 0.958-0.993) and citrate (OR=0.067，95%CIl;0.012-0.376) in 24-hour urine , and 'THP (OR=0.946，95%CI: 0.908-0.986) and OPN(OR=0.896，95%CI:0.803-0.999) in ser-um were the protective factors for urolihiasis , while calcium level ( OR=2.125,95%CI; 1.243-3.633) 24-hour urine was a risk factor( all the P<0.05). ROC curve analysis showed that the areas under the curve ( AUC") for the individual diagnosis of urolithiasis were0.846,0.809,0.786,0.823,0.748 , and 0.755 for the above six iomarkers, respectively.The AUC for the combined diagnosis u-sing THIP+OPN in serum，THP+OPN in 24-hour urime and all the six biomarkers were 0.882,0.920 and 0.984,respectively , indica-ting better diagnostic performance.Conclusion The combined detection of the THP and OPN levels in serum and 24-hour urine mayhave good diagnostic value for urolithiasis and serve as potential diagnostic biomarkers.