〔Abstract〕 Objective To investigate the correlation between subcortical ischemic vascular disease(SIVD) and paraoxonase 1(PON1) gene polymorphism. Methods Sixty-five SIVD patients and 35 medical examiners in the same period were included as SIVD group and control group, respectively. The Fazekas classification and the number of luminal infarcts(LI) were evaluated according to the MRI findings of the head, and the SIVD group was divided into the WML group and the LI group. According to the degree of brain damage, they were divided into mild disease group, moderate disease group and severe disease group. Sanger sequencing method was used to determine the expression of the subject′s PON1 gene at locus 192 and 55 respectively. Results (1) The average age was higher than that of the control group(P<0.05), and the high-density lipoprotein cholesterol(HDL-C) level was lower than that of the control group(P<0.05).There was a statistically significant difference in smoking status between the SIVD group and the control group(P<0.05);(2) The distribution of Q192 R and L55 M genotypes in the SIVD group and the control group conformed to the Hardy-Weinberg equilibrium law;(3) The difference of PON1 gene Q192 R and L55 M genotype distribution between the SIVD group and the control group was statistically significant(χ2=8.780,P<0.05; χ2=4.239,P<0.05). Both the R allele frequency and M allele frequency in the SIVD group were higher than those in the control group(χ2=8.765,P<0.01; χ2=4.926,P<0.05);(4) In the WML group and the LI group, the R allele frequency of the severe disease group was higher than that of the moderate disease group and the mild disease group(P<0.016 7), and the M allele frequency of the moderate disease group and the severe disease group were both higher than that of mild disease group(P<0.016 7);(5) Multivariate Logistic regression analysis showed that age, smoking, and carrying PON1 gene R and M alleles were all independent risk factors for the risk of SIVD(P<0.05). Conclusion The pathogenesis of SIVD may be related to the difference in the expression of the PON1 gene at locus 192 and 55. Carrying R and M alleles at this locus may promote the pathogenesis of SIVD. These findings provide a certain theoretical basis for finding new targets for the prevention and treatment of SIVD.