Ischemic stroke is a leading cause of death and adult disability worldwide. Recent research suggests that renalase is strongly associated with heart disease and hypertension and may play a role in ischemic stroke. In this study, we investigate the genetic association between renalase and ischemic stroke in a northern Chinese Han population. We genotyped single-nucleotide polymorphisms of the renalase gene in 507 ischemic stroke patients and 503 gender-matched controls from a northern Chinese Han population, and we classified these case samples in depth by complications with diabetes or hypertension and by ischemic stroke subtypes. We undertook allele, genotype, and haplotype association studies in all the cases and in the subgroups, as well as multiple factor analysis by logistic regression. rs10887800 and rs2576178 were significantly associated with ischemic stroke with hypertension by logistic regression (p = 0.041 and p = 0.038, respectively). The recessive model showed a strong association of rs2296545 with ischemic stroke patients in hypertension subgroups (OR = 1.927, 95 % CI = 1.012-3.669, p = 0.046). The renalase gene is closely related to ischemic stroke in this northern Chinese Han population, suggesting that renalase may be mechanistically involved in stroke pathology.