CYP1A1 is a metabolizing enzyme and key polymorphisms in its gene may contribute to the risk of ischemic stroke. This study aimed to investigate the association of the rs4646903 and rs1048943 polymorphisms of with stroke risk in a meta-analysis and a bioinformatic approach. An electronic search was conducted and, after the screening procedure, six eligible studies were included in the meta-analysis. Some bioinformatic tools were employed to analyze the effects of rs4646903 and rs1048943 on gene function. There was a significant association between rs4646903 and the reduced risk of ischemic stroke, whereas there was no significant association for rs1048943. analysis showed that rs4646903 and rs1048943 polymorphisms could affect the gene expression and cofactor affinity, respectively. Based on these results, rs4646903 may be a protective genetic factor against ischemic stroke.