Objective To explore the effect of applying bundled intervention combined with closed-loop management in prevention and control of multi-drug resistance bacterial infections (MDRBI) in ICU. Methods A total of 275 EICU patients hospitalized from January to December 2020 were seen as the control group, who received routine management. Another 239 EICU patients hospita-lized from January to October 2021 were assigned into the intervention group, who was subjected to bundled intervention combined with closed-loop management for prevention and control of MDRBI. Results After implementation of bundled intervention combined with closed-loop management, the intervention group had conspicuously lower incidence rate of MDRBI, and significantly shorter hospital stay, than the control group; the implementation rates of 4 nursing indexes (usage of isolation signs, hand hygiene, environmental disinfection, medical staffers′ knowledge level of MDRBI), and the rate of etiology examination were significantly higher in the intervention group than those in the control group （P＜0.05 for all）. Conclusion Application of bundled intervention combined with closed-loop management lowers incidence rate of MDRBI in ICU.