Caspase 7 (CASP7) is located on chromosome 10q25.3 that has been identified to be a susceptibility locus of ischaemic stroke (IS) by genome-wide association study. Elevated CASP7 was observed in IS, acting as a key apoptotic mediator in the development of IS. The aim of this study was to investigate the association between genetic polymorphisms in CASP7 and risk of IS. The CASP7 polymorphisms were genotyped using a TaqMan allelic discrimination assay. The expression levels of CASP7 mRNA were examined using quantitative polymerase chain reaction and luciferase activity was analyzed using the Dual Luciferase reporter assay. The rs12415607 in the promoter of CASP7 was associated with a reduced risk of IS (AA vs. CC: adjusted OR = 0.55, 95% CI: 0.38-0.80, P = 0.002; CA/AA vs. CC: adjusted OR = 0.70, 95% CI: 0.54-0.91, P = 0.007; AA vs. CC/CA: adjusted OR = 0.64, 95% CI: 0.46-0.90, P = 0.01; A vs. C: adjusted OR = 0.74, 95% CI: 0.62-0.89, P = 0.001). Moreover, the rs12415607 AA genotype carriers exhibited lower levels of CASP7 mRNA and the rs12415607 A allele decreased the promoter activity. These findings indicate that the rs12415607 A allele induces lower levels of transcriptional activity and CASP7 mRNA, and thus is associated with a reduced risk of IS.