Apalutamide is a novel competitive inhibitor of the androgen receptor for the treatment of non-metastatic castration-resistant prostate cancer or metastatic castration-sensitive prostate cancer. Rash is the most common skin adverse reaction of apalutamide. If rash is paid insufficient attention, further developing life-threatening Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis. Here, we reported a case of toxic epidermal necrolysis caused by apalutamide. An 86-year-old male patient developed a Nikolsky-positive maculopapular rash, skin exfoliation and mucosal erosion involving 60% body surface area 24 days after treatment of oral apalutamide (180mg/d) for prostate cancer with bone metastases. The skin manifestations aggravated after discontinuation of apalutamide and treatment of methylprednisolone (0.8mg/kg/d) and immunoglobulin (400mg/kg/d) for 2 days. Then, clinician increased the dose of methylprednisolone and immunoglobulin. The skin symptoms improved after treatment of methylprednisolone (1.2mg/kg/d) and immunoglobulin (600mg/kg/d) for 5 days. This is the first to report a dose-dependent response to methylprednisolone and immunoglobulin in the treatment of apalutamide-caused toxic epidermal necrolysis. Since the number of prostate cancer patients treated with apalutamide increases, it is necessary to summarize and analyze the clinical characteristics and treatment experience in cases of severe skin adverse reactions caused by apalutamide.