Epilepsy is a common chronic neurological disease. The International League Against Epilepsy(ILAE)defines seizures as：the transient occurrence of signs or symptoms due to abnormally excessive or synchronous neuronal activity in the brain. About 70% of patients achieve seizure -free with appropriate medical treatment，but nearly one -third of patients still do not respond to current antiepileptic drugs(AED). The alpha subunits of voltage - gated sodium channels(VGSC)are encoded by a highly conserved gene family，of which mutations in SCN1A，SCN2A，and SCN8A genes are important causes of central nervous system diseases. Previous studies have shown that voltage-gated sodium channels play an important role in the pathological process of treatment-resistant epilepsy (TRE). In this review，the concept，pathogenesis and drug resistance mechanism of TRE were introduced in detail，meanwhile the role and mechanisms of VGSC in TRE were reviewed.