Objective To investigate and analyze an outbreak of healthcare-associated infection (HAI) with varicella among health care workers (HCWs), analyze the causes of hospital transmission of varicella zoster virus. Methods Through on-site interview and telephone inquiry, the demographic data, varicella and herpes zoster-rela-ted epidemiological history and vaccination history of HCWs in intensive care unit (ICU) of a hospital from October 5 to December 23, 2020 were investigated, the occurrence and prognosis of varicella and herpes zoster in all ICU patients were investigated, epidemiological characteristics and transmission route were analyzed. Results From October 26 to December 2, 2020, ICU reported 4 cases of varicella infection among HCWs, the outbreak lasted for 38 days. All infected HCWs were ICU nurses, including 2 nurses of ICU, 1 intern nurse and 1 rotation nurse; there are 1 case in the first generation, 2 cases in the second generation and 1 case in the third generation, all patients denied their co-habitation and recent exposure to varicella or herpes zoster cases. A 64-year-old female patient with post-herpetic neuralgia was hospitalized in ICU from September 28 to October 20, at the time of admission, the patient's right waist scattered herpes zoster had scabbed; the first case had cared for patient without wearing gloves. Infection rate of susceptible persons who used lounge-1 72 hours before the eruption of varicella was 66.7%, susceptible persons who used lounge-2 were not infected. This outbreak caused a total direct economic loss of 2 725 Yuan. Conclusion The first case may be caused by nursing a hypo-immunity case of herpes zoster without wearing gloves, and the subsequent case may be the outbreak of varicella caused by inhaling the high concentration of virus particle aerosol formed by respiratory secretions of infected cases in the lounge.