Abstract: OBJECTIVE To explore the effect of cleaning quality management of surgical instruments in central sterile supply department（CSSD） based on structure-process-outcome（SPO） model on prevention of nosocomial infection. METHODS A total of 800 pieces of surgical instruments that were recycled from the First People's Hospital of Lianyungang City were chosen as the study objects and randomly divided into the control group and the study group, with 400 pieces in each group. The control group was treated with basic rinsing for disinfection, while the study group was treated with rinsing for disinfection based on the standards of SPO on basis of the control group. The qualified rate of cleaning, satisfaction with disinfection of surgical instruments and incidence of nosocomial infection were observed and compared between the control group and the study group. RESULTS There was no significant difference in the baseline data between the two groups, and the baseline data were comparable. As compared with the cleaning effect of surgical instruments, the qualified rate of cleaning of the study group was higher than that of the control group, the proportions of satisfaction with disinfection of surgical instruments was higher in the study group than in the control group, the incidence of nosocomial infection of the study group was lower than that of the control group when the surgical instruments were used again, and there were significant differences（P＜0.05）. CONCLUSION The cleaning quality management of surgical instruments in CSSD based on SPO may remarkably raise the qualified rate of cleaning of surgical instruments and reduce the incidence of nosocomial infection, it has positive effect on treatment of patients and prevent the patients from avoidable harms when undergoing surgery.