Rationale:Steven–Johnson syndrome (SJS) is characterized by severe illness, rapid progression, and high mortality rates, with the vast majority of cases induced by medications. Botulinum toxin, a neurotoxin produced by Clostridium botulinum, has not been reported in the literature as a causative agent of SJS.Patient concerns:A 56-year-old male patient, who underwent surgery for cerebral hemorrhage, developed widespread patchy annular papules following the injection of botulinum toxin into the masseter muscle. Some lesions exhibited a target-like appearance, and all major organ systems were affected.Diagnoses:Consider the delayed SJS induced by the combination of carbamazepine and botulinum toxin.Interventions:Intravenous administration of methylprednisolone in conjunction with immunoglobulin is indicated. For ocular lesions, topical treatment includes tobramycin-dexamethasone and sodium hyaluronate eye drops; for ulcerated areas, local application of lactulose-iodoquinol is recommended, while non-ulcerated regions should be treated with halometasone ointment topically.Outcomes:The patient has been discharged, and there has been a noticeable improvement in their symptoms.Lessons:In order to prevent severe adverse reactions, patients using carbamazepine in conjunction with other medications should be vigilant for the early symptoms of serious drug rashes.