Objective To analyze risk factors of nosocomial infection in multiple myeloma patients undergoing chemotherapy, and provide a reference for nursing. Methods A total of 168 patients with multiple myeloma were divided into an infected group (n=80) and an uninfected group (n=88) according to whether they suffered from nosocomial infection during treatment. To analyze the occurrence and risk factors of nosocomial infection in multiple myeloma patients. Results The participants totally received che-motherapy 188 times during hospitalization, the infected group experienced 96 times nosocomial infection, mainly in respiratory and digestive system. Age, diabetes mellitus, the International Staging System stage, the Durie-Salmon stage, and length of hospitalization were the influencing factors of nosocomial infection in multiple myeloma patients (all P<0.05). Conclusion The rate of nosocomial infection in multiple myeloma patients is high, and it is influenced by multiple factors, medical staff should take targeted interventions according to the influencing factors,so as to decrease the incidence of nosocomial infection, and improve prognosis.