Abstract: OBJECTIVE To investigate the clinical factors and anti-infective analysis of nosocomial infection in patients with chronic hepatitis B infection, so as to provide evidence for clinical treatment. METHODS Clinical data of 200 cases of chronic hepatitis B patients from Apr. 2012 to Apr. 2015 in our hospital receiving treatment were retrospectively analyzed. They were divided into infection group with 80 cases and control group with 120 cases according to nosocomial infection , and relevant factors for nosocomial infections were analyzed. RESULTS The hospital stay of patients in infection group was higher than that in control group, the white blood cells and cholinesterase were lower than those of control group , and the differences were significant (P<0.05). The multivariate analysis showed that the patient's hospital stay, invasive procedures, drinking history, low WBC, complications and hypoalbuminemia were independent risk factors of nosocomial infection in patients with chronic hepatitis B (P<0.05), and application of antiviral drugs was the factor to protect patients from infection. CONCLUSION There are many risk factors causing nosocomial infection in patients with chronic hepatitis B patients, and application of antiviral drugs was the factor to protect patients from infection.