Conventional medical therapies have not been very successful in treating adults with refractory septic shock. The effects of direct hemoperfusion using polymyxin B and veno-arterial extracorporeal membrane oxygenation (ECMO) for refractory septic shock remain uncertain. A 66-year-old man was admitted to the emergency department and suffered from sepsis-induced hemodynamic collapse. For hemodynamic improvement, we performed direct hemoperfusion using polymyxin B. Computed tomography scan of this patient revealed emphysematous pyelonephritis (EPN), for which he underwent emergent nephrectomy with veno-arterial ECMO support. To the best of our knowledge, this is the first report of successful treatment of EPN with refractory septic shock using polymyxin B hemoperfusion and nephrectomy under the support of ECMO.