Focal segmental glomerulosclerosis (FSGS) often leads to refractory nephrotic syndrome (NS). A high level of low-density lipoprotein (LDL) is a risk factor for the progression of NS. An 8-year-old girl presented with severe proteinuria refractory to steroid therapy. She was diagnosed with non-IgA diffuse mesangial proliferative glomerulonephritis. Oral prednisolone, methylprednisolone (mPL) pulse therapy, and cyclosporine and cyclophosphamide therapy failed to achieve remission. Follow-up renal biopsy revealed FSGS. Her serum level of LDL was high, and LDL-apheresis (LDL-A) was performed five times, followed by mPL pulse therapy. Urinary protein decreased from 2-4 g x day(-) to 0.5-1.0 g x day(-). LDL-A may be beneficial in the treatment of multidrug-resistant FSGS.