Abstract: Objective To investigate the risk factors of multiple drug-resistant infections(MDRO) in neonatal intensive care unit (NICU), and to provide scientific evidence for clinical prevention and control measures. Methods From January, 2012 to December, 2016 in Hainan Province Maternal and child health hospital treated 326 cases of NICU infection in children, according to the results of drug sensitive test for MDRO infection group (102 cases) and non MDRO infection group (224 cases), analysis of prevalence of multidrug-resistant bacteria. Single factor and multi factor Logistic regression analysis were used to analyze the risk factors of NICU multiple drug-resistant infections. Results From 2012 to 2016, the number of NICU multiple drug-resistant infections in our hospital showed an increasing trend year by year. One hundred and fifty-six strains of MDRO were detected in 102 children with MDRO infection. The number of MDRO detected in the top three was MDR/PDR-PA 60strain (38.46%), MRSA 45 strain (28.85%), CR-AB 37 strain (23.72%). The main sites of MDRO infection are respiratory tract infection and bloodstream infection. Univariate and multivariate Logistic regression analysis showed that birth weight (OR=2.581, P=0.026), coma (OR=3.846, P=0.038), invasive mechanical ventilation (OR=4.317, P<0.001), types of antibacterial drugs (OR=5.218, P<0.001) and antimicrobial use time (OR=2.615, P=0.032) were independent risk factors multiple drug-resistant infections in NICU. Conclusion There are many risk factors for multiple drug-resistant infections in children with NICU, and prevention and control measures should be taken as early as possible to reduce the incidence of multiple drug-resistant infections.