Introduction: Epilepsy is one of the most common disorders of the brain, affecting at least 50 million persons worldwide. Despite a variety of current antiepileptic drugs, research for discovering new drugs with more efficacies and less side effects has been continued. Herbal medicine has various natural substances and proper context for this type of research. The aim of this study was to investigate the effect of Humulus lupulus (Hops) extract on seizure attacks in an experimental animal model. Materials and Methods: 40 male mice have been chosen randomly and divided into 5 groups including control group, sham group, and three experimental groups. Treated mice received aqueous extract of Humulus lupulus via gavage at doses of 200, 400, and 600 mg/kg for 4 weeks. Thirty minutes after gavage with different doses of the herb or distilled water (sham mice), pentylenetetrazole (PTZ 45mg/kg) was injected intraperitoneally. Animals immediately transferred to a special cage and the seizure behaviors were recorded by a camera during a 25 minutes period. Results: Data analysis indicated that the aqueous extract of Humulus lupulus had a significant inhibitory effect on PTZ-induced seizure. Treatment with Humulus lupulus significantly increased the latency of seizure onset, decreased the intensity of seizure, and seizure duration. Conclusion: The attained results showed that Hops extract has anticonvulsant effect on PTZ-induced seizure and may be useful for treatment of epilepsy.