PurposeThis report sheds light on a successful treatment in febrile infection-related epilepsy syndrome (FIRES) with the combined use of lidocaine and MgSO4.MethodsWe report a 12-year-old previously healthy girl who experienced an upper respiratory infection with fever and headache for 2 days, then suddenly went into a coma followed by repetitive status epilepticus. All tests for CNS infection, metabolic and toxic diseases, and autoimmune encephalitis were negative. Hence, the diagnosis of FIRES was made. During 5 weeks of hospital treatment, various antiepileptic drugs were administered at different times without success. To achieve seizure control, we then attempted the use of lidocaine first, then followed by MgSO4.ResultsThe SE was successfully controlled when lidocaine plus MgSO4 was introduced. At follow-up, almost no neurological sequelae remained.ConclusionThis is the first report describing the combined use of lidocaine and MgSO4 with successful treatment outcomes. This experience has indicated that even FIRES can be controlled if treated promptly with certain agents. However, more studies are needed to explore the mechanisms and effects of lidocaine and MgSO4 in FIRES.