Abstract: OBJECTIVE To investigate the distribution and drug resistance of pathogens causing nosocomial infection in the patients with chronic hepatitis B (CHB) so as to put forward effective anti-infection programs. METHODS A total of 81 CHB patients who were complicated with nosocomial infection and treated in Quanzhou First Hospital Affiliated to Fujian Medical University from Apr 2015 to May 2018 were enrolled in the study. The incidence of infection and etiological characteristics were observed. RESULTS The patients with abdominal infection, lower respiratory tract infection, upper respiratory tract infection and blood infection were dominant among the CHB patients complicated with nosocomial infection. Totally 98 strains of pathogens were isolated from specimens, 72 (73.47%) of which were gram-negative bacteria, 20 (20.41%) were gram-positive bacteria, and 6 (6.12%) were fungi. The major species of gram-negative bacteria were highly resistant to the antibiotics such as ampicillin, while the strains were sensitive to cefoxitin. The major species of gram-positive bacteria were highly resistant to the antibiotics such as penicillin G, while the strains were sensitive to piperacillin-tazobactam. The fungi were highly resistant to the antibiotics such as fluconazole, while the strains were sensitive to 5-fluorocytosine. CONCLUSION The gram-negative bacteria are dominant among the pathogens isolated from the CHB patients complicated with nosocomial infection and are highly drug-resistant. It is necessary for clinicians to pay close attention to the progress of illness and reasonably choose antibiotics for treatment of infection based on the result of drug susceptibility testing.