Cortico-subcortical networks are considered core pathologic substrates for frontal lobe epilepsy with generalized tonic clonic seizures; however, the mechanism is still unknown. This study aims to identify the changes of cortico-subcortical networks by resting-state functional connectivity. 60 patients with frontal lobe epilepsy and healthy controls were enrolled. Bilateral hemispheres were divided into 5 nonoverlapping cortical lobes. Functional connectivity between each cortical lobe and the subcortical regions were calculated, and functional connectivity strength was used to evaluate the interconnectivity. Our results indicate that the decrease connection between prefrontal cortex and subcortical structures suggests it maybe the epicenters of frontal lobe epilepsy.