OBJECTIVE：To observe the efficacy and safety of methylprednisolone combined with entecavir in the treatment of primary nephrotic syndrome with hepatitis B virus infection. METHODS： 23 primary nephrotic syndrome patients with hepatitis B virus infection were given 0.5 mg/times Entecavir tablet， orally， once a day， for 2 weeks， and added 0.8mg/（kg.d） Methylprednisolone tablet， orally， once a day， for 8 weeks， then the dose was maintained for 2-3 months every other day， and then decreased 4 mg for 4 weeks every other day， and the dose was decreased 4 mg every 2-4 weeks， until drug withdrawal. Entecavir tablet was used in the whole process of Methylprednisolone tablet， the dose was adjusted and gradually stopped based on HBV-DNA within 3 months of Entecavir tablet withdrawal. Liver and renal efficacy， 24 h urine protein excretion， serum albumin （ALB）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST） levels before and after treatment of 2，6，12 and 15 months， and the incidence of adverse reactions of all patients were observed. RESULTS： The liver and renal efficacy were 100％； after treatment of 2， 6， 12 and 15 months， 24 h urine protein， ALT and AST were significantly lower than before and gradually decreased by time， ALB was significantly higher than before and gradually increased by time， the differences were statistically significant （P＜0.05）； the incidence of adverse reactions was 43.48％， and there were no obvious adverse reactions and no renal dysfunction. CONCLUSIONS： Methylprednisolone combined with entecavir has significant efficacy in the treatment of primary nephrotic syndrome with hepatitis B virus infection， with good safety.