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Objective To observe the clinical efficacy of staphylococcal protein A immunoadsorption plus nonmyeloablative chemotherapy with CD34+ autologous peripheral blood stem cell transplantation in the treatment of refractory systemic lupus erythematosus (SLE). Methods Three patients with active SLE were enrolled into this study. All patients were diagnosed with lupus nephritis by renal biopsy and poorly responded to routine therapy. Before transplantation, patients were given 6 sessions of immunoadsorption apheresis using columns of staphylococcal protein A-silica with an interval of 3 days; each session processed 3 L plasma and a total of 18 L plasma was processed over the 6 treatments. Three days following the immunoadsorption apheresis, the mobilization of stem cells was realized by intravenous cyclophosphamide at a dose of 2 g per square meter of body surface area and subcutaneous recombinant human granulocyte colony-stimulating factor (G-CSF) at a dose of 5 g per kilogram of body weight per day for 5 days. Then, peripheral blood raonoclonal cells were obtained by CS-3000 Cell Separator, and passed through the Clini Macs CD34+ cell selection device, with the final concentration of CD34+ cells being 2.6×106, 2.1×106 and 2.4×106 per kilogram of body weight respectively, and that of CD3+ cells being 3×105, 2.1×105, and 2.0×105 per kilogram of body weight, respectively, in these three patients. The conditioning regimen consisted of oral fludarabine of 50 mg/d for 5 days plus intravenous pig anti-human thymocyte immunoglobulin (ATG) at a daily dose of 90 mg/kg for 5 days. After 72-hour treatment with ATG, the frozen stem cells were infused back to the patients. Clinical manifestations and lupus-correlated immune parameters were compared in patients at baseline and after transplantation. Results Following immunoadsorption apheresis, an obvious decrease was observed in the level of serum anti-dsDNA, antinuclear antibody and IgG antibodies, while an increase in the level of serum complement 3. All patients achieved the reconstruction of hemopoiesis 2-3 days after the transplantation. Also, an apparent clinical remission was achieved with the SLEDAI score being less than 3. Six months after the transplantation, serum anti-dsDNA and antinuclear antibodies as well as urine protein were undetectable, the level of complement 3 reached the normal range, and renal function was restored. Conclusions Staphylococcal protein A immunoadsorption plus nonmyeloablative CD34+ autologous peripheral blood stem cell transplantation are effective and safe for refractory SLE, but the long-term effect remains to be connfirmed by further studies.