Toxic epidermal necrosis (TEN) is rare and can be life-threatening for patients. Appropriate management of TEN patients could give optimal results and prevent complications. One treatment modality for TEN is plasmapheresis, which is rarely available in most cases with severe TEN. Here we reported a successful treatment of severe TEN with plasmapheresis. A 40-year-old woman under tuberculosis therapy complained of shortness of breath that began four days prior to hospital admission and worsened ever since. The patient's skin was peeling with red spots and rashes all over the body for a week. During the examination, the patient was compos mentis, and the SCORTEN score was 2 with 12.1% risk of mortality rate. Dermatological examination of the face, trunk and extremities found extensive erosions, loose bullae filled with clear fluid, brown crusts, and generalized distribution with more than 30% epidermolysis. The patient was diagnosed with toxic epidermal necrolysis caused by antituberculosis therapy. We treated the patient by discontinuing the suspected drugs and administering the corticosteroids, but no improvement was observed. The patient underwent two cycle plasmaphereses with 5% albumin, resulting in 1.2 liter of plasma exchange. Re-epithelialization was observed after three days, and the patient was discharged on day 8. This case-report highlights the important role of plasmapheresis in treating the TEN patients. However, a study with larger sample sizes is warranted to validate the efficacy of plasmapheresis in TEN.