Objective To explore the application efficacy of failure mode and effect analysis(FMEA)in reducing multidrug-resistant infection (MDRO) in intensive care unit (ICU). Methods A special improvement team with the participation of ICU, healthcare-associated infection (HAI) department and general affairs department was set up, through investigation on current situation and implementation of a series of improvement and intervention measures, non-compliance rate of MDRO prevention and control measures and the discovery rate of MDRO HAI before and after the implementation of FMEA were compared. Results The non-compliance rate of MDRO prevention and control measures decreased from 31.99% (111/347) before the implementation of project to 6.07% (44/725) after the implementation, the discovery rate of MDRO HAI decreased from 19.89 ‰ (95/4 776) before the implementation of the project to 9.73 ‰ (46/4 728) after the implementation, differences were both statistically significant (both P < 0.05). Conclusion Combined with the current situation, application of FMEA quality improvement tool can effectively reduce MDRO infection rate in ICU. However, due to the difference in specimen detection rate, further research on HAI rate cannot be carried out, the follow-up research will focus on the MDRO specimen detection rate of large specimens in China.