Abstract: Objective To explore the efficacy and safety of leflunomide and methylprednisolone combined with entecavir for the treatment of HBV-associated glomerulonephritis(HBV-GN). Methods Thrity-seven patients hospitalized with HBV-GN from January,2014 to December,2015 were selected;all of them were confirmed with HBV-GN based on renal biopsy;Twenty-one patients were assigned to the treatment group to receive treatment with leflunomide and methylprednisolone combined with entecavir,and 16 patients were assigned to the control group to receive entecavir antiviral treatment alone.Patients in the two groups were compared for reduction in urine protein,ALT and HBV-DNA load at 3 and 6 months of treatment. Results After 3 months of treatment,the urine protein level in the treatment group was (1.76±1.20) g/24 h,which was significantly better than (2.70±1.50) g/24 h in the control group(P<0.05);at 6 months of treatment,the urine protein level in the treatment group was(1.61±0.90) g/24 h,which was significantly better than(2.34±1.20) g/24 h in the control group(P<0.05);there was no significant difference between the two groups in ALT(17.0±6.3) U/L in treatment group compare with (19.7±4.0) U/L in control group(P>0.05);by 3 months of antiviral treatment,HBV-DNA load had normalized in patients in both groups upon monitoring;there was no significant difference between the two groups in ALT(19.0±4.7) U/L in treatment group against (18.3±4.4) U/L in control group(P>0.05);and HBV-DNA load had normalized in both groups. Conclusion As the therapeutic approach for HBV-GN remains controversial in clinical practice,the patient would typically develop into ESRD within several years due to uncontrolled urine protein,which could markedly decline the patient's quality of life or even be life-threatening,and has been a heavy burden on the national medical insurance system.Considering that the efficacy and safety of leflunomide and methylprednisolone combined with entecavir for the treatment of HBV-GN remain unclear,this study is expected to provide more evidences for the management of HBV-GN.