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Background: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN) is one of severe cutaneous adverse reactions with low morbidity but high mortality. Different systemic immunomodulating treatments are proposed but still remain controversial. Tumor necrosis factor (TNF)-alpha is long thought to be a vital mediator of epithelial cell death in SJS-TEN, indicating a potential target for therapy. Objective: The aim of this systemic review is to evaluate the efficacy and safety of biologic TNF-alpha inhibitors in the treatment of SJS-TEN. Methods: We reviewed the published literature by searching from PubMed, EMBASE, Web of Science and ClinicalTrial.gov. A total of 27 articles fulfilling our inclusion criteria were found and analyzed. Results: There were 21 case reports, four case series and two randomized controlled trials (RCTs) on the biologic TNF-alpha inhibitors for SJS-TEN therapy, comprising 91 patients. TNF-alpha inhibitors were used as monotherapy, second-line therapy or combination therapy. Among them, 79 patients (86.8%) responded well and discharged with few side effects and complications. Conclusions: Biologic TNF-alpha inhibitors are a safe and effective treatment for SJS-TEN. But further, larger RCTs need to be conducted to provide more evidence for clinical application.