Etiology of the idiopathic childhood stroke remains unknown. In previous studies, the immunologic process may be involved in the idiopathic stroke. Tumor necrosis factor- alpha (TNF-alpha), an important immune mediator, may contribute to the initiation and progression in the stroke. The main purpose of this study was to investigate correlation of TNF-alpha genetic variation and idiopathic childhood ischemic stroke. Using the direct DNA sequencing method, polymorphisms in the TNF-alpha promoter region were genotyped in 67 Chinese patients with idiopathic childhood stroke and 70 controls. Among totally 7 single nucleotide polymorphisms identified in the TNF-alpha promoter region, the variant of the -863C/A is associated with increased risk of idiopathic childhood ischemic stroke in our study group. TNF-alpha molecule may have genetically as well as functionally an important role in the pathogenesis of idiopathic childhood ischemic stroke in the Chinese population.