To investigate the prevalence of hepatitis B virus (HBV) infection in systemic lupus erythematosus (SLE) patients in southern China, SLE inpatients were retrospectively investigated for their HBV infection rate. Fifteen SLE patients positive for hepatitis B surface antigen (HBsAg) were followed up. Furthermore, serum interferon (IFN)-α levels among SLE patients were detected by ELISA. Results showed estimated HBsAg-positive rate was 10.74% in general population. The HBsAg-positive rate was lower in SLE patients compared with controls (2.33 vs. 9.57%, P < 0.01). Interestingly, 13 out of 15 SLE patients converted from HBsAg positive to HBV surface antibody (HBsAb) positive even under glucocorticoid therapy. In addition, we found significantly increased IFN-α levels in SLE patients.The prevalence of HBV infection in SLE patients was lower than that in sex- and age-matched non-SLE controls in southern China. The characteristic IFN signatures in SLE may favor the subsequent clearance of HBV.