Aim To investigate the relationship between single nucleotide polymorphism (SNP) of Cathepsin D(CTSD)gene promoter and acute myocardial infarction (AMI) and its related risk factors. Methods The CTSD gene promoters of 357 AMI patients and 347 control population were amplified and sequenced by polymerase chain reaction in case-control study, combined with the sequence and comparison of DNA sequencing, SNP was searched in NCBI database for data statistics and analysis. After using the Hardy Weinberg balance test, the χ² test and t test were used for correlation analysis. Logistic regression was used to analyze the association of multiple risk factors and two SNP loci with susceptibility to AMI. Linkage unbalance and haplotype analysis were performed using Haploview4.2 software and SHEsis online software. TRANSFAC database was used to predict the binding sites of transcription factors that may be affected by SNP. Results Logistic regression analysis showed that age increase, smoking history, hypertension history and triglyceride increase were independent risk factors for AMI (P＜0.05), which significantly increased the risk of acute myocardial infarction. High density lipoprotein and cholesterol are protective factors of AMI (P＜0.05), which can significantly reduce the risk of AMI. This result may be related to the use of lipid-regulating drugs in the myocardial infarction group, which requires further analysis by expanding samples. The two SNP in the promoter sequence of CTSD gene were not associated with AMI. The linkage disequilibrium and haplotype analysis suggested that the two SNP loci were in the same linkage disequilibrium region (D′=1.000, R²=0.978), and haploid did not increase AMI susceptibility (P＞0.05). Conclusion The two SNP in the promoter region of CTSD gene are completely linked disequilibrium. The two SNP and their haploid types were not associated with the incidence of AMI, but provided the population genetic data of CTSD gene promoter region polymorphism.