HSPA8 is involved in many stroke-associated cellular processes, playing a pivotal role in the protein quality control system. Here we report the results of the pilot study aimed at determining whetherHSPA8SNPs are linked to the risk of ischemic stroke (IS). DNA samples from 2139 Russians (888 IS patients and 1251 healthy controls) were genotyped for tagSNPs (rs1461496, rs10892958, and rs1136141) in theHSPA8gene using probe-based PCR. SNP rs10892958 ofHSPA8was associated with an increased risk (risk allele G) of IS in smokers (OR = 1.37; 95% CI = 1.07–1.77;p= 0.01) and patients with low fruit and vegetable consumption (OR = 1.36; 95% CI = 1.14–1.63;p= 0.002). SNP rs1136141 ofHSPA8was also associated with an increased risk of IS (risk allele A) exclusively in smokers (OR = 1.68; 95% CI = 1.23–2.28;p= 0.0007) and in patients with a low fruit and vegetable intake (OR = 1.29; 95% CI = 1.05–1.60;p= 0.04). Sex-stratified analysis revealed an association of rs10892958HSPA8with an increased risk of IS in males (risk allele G; OR = 1.30; 95% CI = 1.05–1.61;p= 0.01). Thus, SNPs rs10892958 and rs1136141 in theHSPA8gene represent novel genetic markers of IS.