Objective To develop a graded risk prevention program for central venous catheter occlusion and evaluate its application effect.Methods From May to August 2023, 149 patients were assigned to the control group and received conventional central venous catheter insertion, fixation, and maintenance; from September to December 2023, 151 patients were assigned to the observation group and were subjected to a graded risk prevention program for central venous catheter occlusion, which was developed based on a risk prediction model, evidence summaries, and expert panel discussions.The incidence of central venous catheter occlusion, catheter indwelling time, and nurses′ knowledge awareness rate regarding the prevention and management of catheter occlusion were compared between the two groups before and after the intervention.Results After the intervention, the incidence of catheter occlusion in the observation group was lower than that in the control group, but the P-value was close to the critical value (0.05); the average catheter indwelling time of the observation group was significantly longer than that of the control group (P＜0.05); after applying the program, the knowledge of prevention and treatment of central venous catheter occlusion among nurses was significantly improved (P＜0.05).Conclusion The application of a graded risk prevention program for central venous catheter occlusion can extend the catheter indwelling time, and enhance the awareness of nursing staff in preventing catheter occlusion risks.However, the impact on catheter occlusion rates requires further investigation with a larger sample size to confirm.