Hypoxia-inducible factor 1 A (HIF1A) is considered as a potential marker gene for ischemic stroke (IS), its gene polymorphism may affect IS risk and may be related to the IS pathological process. In this study, a total of 159 IS patients and 141 healthy controls were enrolled by case-control study method. HIF1A three single nucleotide polymorphisms (SNPs: rs10873142, rs11549465, rs11549467) were genotyped by SNaPshot method and HIF1A protein levels was detected by enzyme-linked immunosorbent assay (ELISA), then the correlation between HIF-1 A SNPs and IS was analyzed by statistical analysis method. The genotype of HIF1A SNPs can affect the expression levels of clinical and laboratory parameters in IS patients, such as high-density lipoproteincholesterol (HDL-C), apolipoprotein A1, reactive oxygen species (ROS). HIF1A TCG haplotype is a protective factor for IS, HIF1A CCG haplotype is a risk factor for IS. However, the association between HIF1A rs10873142, rs11549465, rs11549467 genotypes and the IS risk was not statistically significant. ELISA analysis showed that the HIF1A expression of IS patients is higher than the healthy controls. Therefore, the gene polymorphism and expression of HIF1A may be related to IS pathological process, but the relationship between HIF1A gene polymorphism and the IS risk still needs further study.© 2025. The Author(s).