A 59-year-old man (case 1) with multiple sclerosis (MS) presented with shortness of breath and general fatigue. He had been treated using interferon β-1b (IFNβ-1b) since he was 51 years of age. Laboratory test results showed hypoproteinemia and hypoalbuminemia, proteinuria, and absence of hematuria. He was diagnosed with nephrotic syndrome, and the administration of IFNβ-1b was stopped. Percutaneous renal biopsy was performed, and the histology revealed membranous nephropathy. A 33-year-old woman (case 2) with MS, who had been treated using IFNβ-1b for 7 years, was diagnosed with proteinuria during a medical checkup. She was referred to a nephrologist and was found to have hypoalbuminemia and proteinuria. A diagnosis of nephrotic syndrome was made, and IFNβ-1b therapy was stopped. The patient underwent percutaneous renal biopsy, and the histology revealed membranous nephropathy. Both patients were treated using intravenous methylprednisolone followed by oral prednisolone. Case 1 was administered ciclosporin orally, and his clinical symptoms and laboratory test results improved at first, but his laboratory test results subsequently showed recurrence of proteinuria. Case 2 was administered mizoribine orally, resulting in improvement in clinical symptoms and laboratory test results. Case 2 showed relapse of multiple sclerosis, but the symptoms were mild and were alleviated after steroid therapy. IFNβ therapy has several complications including nephropathy. Previously, several cases of nephrotic syndrome associated with IFNβ within 2 years of therapy were reported, but drug-induced nephropathy could appear after several years of the therapy as our cases. We should pay attention to nephrotic syndrome under using long-term IFNβ.