This study investigates the role of cellular senescence in focal cortical dysplasia type II (FCDII), a common cause of pediatric drug-resistant epilepsy. FCDII is characterized by somatic mosaicism due to post-zygotic mutations in genes of the PI3K-AKT-mTOR pathway, leading to the formation of dysmorphic neurons (DNs) and balloon cells (BCs). The authors found a correlation between epileptiform activity in acute cortical slices from human FCDII brain tissues and the density of dysmorphic neurons. These pathological cells exhibited multiple signatures of cellular senescence, including p53/p16 expression, senescence-associated secretory phenotype (SASP), and senescence-associated β-galactosidase (SAβGal) activity. Administration of senolytic drugs (dasatinib/quercetin) reduced the load of senescent cells and decreased seizure frequency in an *Mto1*^*D2215F*^ FCDII preclinical mouse model, providing evidence that senotherapy may be a promising approach to control seizures in FCDII. These findings suggest that selectively targeting mutated senescent cells in FCDII brain tissue could be a therapeutic strategy.This study investigates the role of cellular senescence in focal cortical dysplasia type II (FCDII), a common cause of pediatric drug-resistant epilepsy. FCDII is characterized by somatic mosaicism due to post-zygotic mutations in genes of the PI3K-AKT-mTOR pathway, leading to the formation of dysmorphic neurons (DNs) and balloon cells (BCs). The authors found a correlation between epileptiform activity in acute cortical slices from human FCDII brain tissues and the density of dysmorphic neurons. These pathological cells exhibited multiple signatures of cellular senescence, including p53/p16 expression, senescence-associated secretory phenotype (SASP), and senescence-associated β-galactosidase (SAβGal) activity. Administration of senolytic drugs (dasatinib/quercetin) reduced the load of senescent cells and decreased seizure frequency in an *Mto1*^*D2215F*^ FCDII preclinical mouse model, providing evidence that senotherapy may be a promising approach to control seizures in FCDII. These findings suggest that selectively targeting mutated senescent cells in FCDII brain tissue could be a therapeutic strategy.