Objective To explore the correlation and clinical significance of the serum Sclerostin（SOST）and Dickkopf-1（Dkk-1）in the progression of idiopathic osteonecrosis of the femoral head（IONFH）. Methods 76 patients with idiopathic ONFH admitted to the Nanjing Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Nanjing University of Chinese Medicine from January 2017 to June 2020 were included as the experimental group. Meantime, healthy people with sex, age (±1 year) and BMI (±1 kg/m2) matched with the experimental group were selected as the control group (n=76). Blood samples were collected from fasting vein to detect and analyze the serum SOST and Dkk-1 levels. Results The serum SOST concentration of patients with ONFH was 1.75 (1.09～2.36) ng/mL, which was significantly higher than the control group 1.42 (0.66～1.87) ng/mL, P= 0.001. The serum Dkk-1 concentration of patients with ONFH was 2.87 (2.03～3.64) ng/mL, significantly higher than the control group 1.86 (1.17～2.41) ng/mL,P=0.000, the difference was statistically significant. The expression of serum Dkk-1 in patients with ONFH was positively correlated with the ARCO stage of ONFH (r=0.341, P=0.003). The expression of serum SOST and Dkk-1 was positively correlated (P＜0.05). ROC curve analysis showed that the sensitivity of serum SOST in the diagnosis of ONFH was 51.30%, and the specificity was 70.05%. The sensitivity of serum Dkk-1 in the diagnosis of ONFH was 80.30%, and the specificity was 63.90% (P＜0.05). Conclusion The serum SOST and Dkk-1 play an important role in the occurrence and development of ONFH, and are closely related to the progression of the disease. They might be an important indicators for predicting the occurrence and development of ONFH and potential targets for the treatment of ONFH.