Objective To explore the risk factors of central venous catheter (CVC) occlusion,and to establish and verify its risk prediction model. Methods A total of 440 patients with CVC were selected and divided into a modeling group (330 cases) and a validation group (110 cases) chronologically. The modeling group was classified according to whether the catheter was occluded, then the risk factors of occlusion were analyzed using univariate and multivariate logistic regression, and a risk prediction model of CVC occlusion was established. The H-L test and ROC curve were used to evaluate the prediction effect of the risk prediction model. Results Multivariate logistic regression analysis showed that, thrombosis history, diabetes, D-dimer and parenteral nutrition were independent risk factors for CVC occlusion. The risk prediction model was Y=3×thrombosis history+1×diabetes+1×D-dimer (≥0.5 mg/L)+1×parenteral nutrition. The area under the ROC curve of the modeling group was 0.745, and the H-L test result showed χ2=9.411,P=0.309 .The area under the ROC curve of the validation group was 0.750, H-L test result revealed χ2=14.263,P=0.075. Conclusion History of thrombosis, diabetes, D-dimer, and parenteral nutrition are independent risk factors for CVC occlusion. The established risk prediction model has good identification and predictive performance, and it can provide reference for clinical prevention of CVC occlusion.