Objective To analyze the correlation between antimicrobial use density (AUD) and change in antimicrobial resistance rate of Stenotrophomonas maltophilia(SM), and explore the influencing factors of antimicrobial resistance of SM. Methods Antimicrobial resistance rate of SM and AUD of commonly used antimicrobial agents in patients in a hospital from 2012 to 2017 were summarized, correlation was analyzed with Pearson correlation method. Results A total of 23 994 strains of gram-negative bacteria were isolated, of which 1 331 strains (5.55%) were SM, mainly from sputum (54.02%) and distributed in intensive care unit (21.49%). Resistance rates of SM to ceftazidime, levofloxacin, and compound sulfamethoxazole were 21.79%, 7.66%, and 13.37% respectively, resistance rates to levofloxacin showed an increasing trend year by year (P<0.05). Resistance rate of SM to levofloxacin was positively correlated with the use intensity of β-lactamase inhibitors, carbapenems, fluoroquinolones, and oxazolidinones (all P<0.05); resistance rate to compound sulfamethoxazole was positively correlated with the use intensity of macrolides (P<0.05). Conclusion Change in resistance rates of SM to levofloxacin and compound sulfamethoxazole are positively correlated with the use intensity of some commonly used antimicrobial agents, reducing AUD is beneficial to the control and reducing of the resistance of SM.