Objective To evaluate the potential association of serum irisin and sclerostin with the development of cardiac valve calcification (CVC) in maintenance hemodialysis (MHD) patients. Methods A retrospective analysis of patients with MHD 150 cases from January 2020 to December 2020 in the dialysis center of the Affiliated Hospital of Southwest Medical University. Clinical data were collected and cardiac color Doppler ultrasound examination were used to assess the calcification of cardiac valves and enzyme-linked immunosorbent assay (ELISA) were applied to measure the serum irisin and sclerostin. Patients were divided into calcification group (n=49) and non-calcification group (n=101) according to the presence or absence of cardiac valve calcification in cardiac color Doppler ultrasound examination. Logistic regression analysis method was used to analyze the related risk factors of CVC. The clinical data, general biochemical indexes and the serum irisin and sclerostin between the two groups were compared. Results The prevalence of CVC in 150 MHD patients was 32.7% (49/150). The ages, the prevalence of diabetes, the age of dialysis, the level of C-creative protein, corrected serum calcium, serum phosphorus, calcium phosphorus products, total cholesterol (TC), triglycerides (TGs), low density lipoprotein cholesterol (LDL-C), sclerostin were higher and the level of serum magnesium and irisin were lower than those in the non-calcification group. The differences were statistically significant between the two groups (P＜0.05). Logistic regression analysis showed that age (OR=1.080, P=0.001), the age of dialysis (OR=1.020，P=0.010), the level of low density-lipoprotein cholesterol (OR=2.249,P=0.005), calcium (OR=1.286，P=0.042), phosphorus (OR=1.188，P=0.002) and sclerostin (OR=1.124,P=0.046) were independent risk factors for CVC and serum irisin(OR=0.993,95% CI=0.987-0.998，P=0.012) was a protective factor for CVC. Conclusion Levels of serum irisin and sclerostin are associated with the formation of CVC in MHD patients. Logistic regression analysis shows that serum sclerostin is an independent risk factor, and serum irisin may be a protective factor in the development of CVC in MHD patients.