Hyperpolarization activated cyclic nucleotide-gated (HCN) channels underlie hyperpolarization-activated current (I_h) generation, regulating spontaneous rhythm and neural oscillation. HCN1 channels are abundantly expressed in the cerebral cortex, hippocampus and brain stem and are suggested to be involved in the initiation and propagation of spontaneous generalized seizure, however, the functional mechanism is still unknown. In this study, to clarify the role of HCN1 channel in induction of epileptic seizure, we performed the chemically- and electrically-induced seizure tests using Hcn1 knock-out (Hcn1-KO) rats. Pilocarpine and 4-aminopyridine produced significantly higher seizure induction in Hcn1-KO rats than in control (F344) rats. Hcn1-KO rats also showed higher sensitivity to electrical shock-induced seizures. In addition, we performed the immunohistochemical analysis of c-Fos expression following electrical shock-induced seizures. Hcn1-KO rats showed a significantly higher Fos expression than control rats in the cerebral cortex and amygdala. These results suggest that HCN1 channels play a crucial role in controlling the susceptibility to epileptic seizure, implying that hyperactivation of the cerebral cortex and amygdala is involved in the enhancement of seizure susceptibility due to loss of HCN1 channel.