Objective  To explore the relationship between C-reactive protein (CRP) clearance and vascular calcification (VC) in native arteriovenous fistulas (AVF) in maintenance hemodialysis (HD) patients.  Methods A total of 136 patients who underwent fistula repair or primary fistula creation for chronic kidney disease (CKD) stages 4-5 at Dingzhou People's Hospital between February 2019 and April 2023 was studied. Patients were grouped into no VC (54 cases), mild-moderate VC (52 cases), and severe VC (30 cases). Clinical features were screened using LASSO regression. Multifactorial logistic regression identified risk factors, built a predictive model, and evaluated its performance. Correlations were analyzed with multiple linear regression, and dose-response relationships were assessed using restricted cubic splines (RCS) and threshold effect analysis. Results  LASSO regression identified age, diabetes, stage 2 hypertension, 24-hour urine volume, calcium-phosphate product, CRP clearance, vascular smooth muscle cell (VSMC) calcium content, and alkaline phosphatase (ALP) activity as predictive factors. Multifactorial logistic regression showed that age (OR=3.062,95% CI:1.131～9.120, P<0.001), diabetes (OR=1.851,95% CI:1.023～3.447, P=0.022), calcium-phosphate product (OR=2.341, 95% CI:1.052～6.076, P=0.005), CRP clearance (OR=0.356, 95% CI:0.123～0.507, P=0.001), VSMC calcium content (OR=1.904, 95% CI: 1.264～5.213, P=0.014), and ALP activity (OR=2.197, 95% CI:1.347～4.280, P=0.010) were independent risk factors for severe VC. The model demonstrated good discrimination (post-validation sensitivity 90.00%, specificity 80.19%), with an accuracy of 82.35% and Youden index 0.702. CRP clearance was negatively correlated with VSMC calcium content  (β=   -0.332, P=0.008) and ALP activity (β=-0.303, P=0.012). A nonlinear relationship was found between CRP clearance and severe VC risk (nonlinearity test P<0.001), with a CRP clearance inflection point at 24.5%.  Conclusion  CRP clearance is associated with AVF-VC in maintenance HD patients and can serve as a biomarker for monitoring AVF-VC.