Aim To investigate the correlation between rs3732378 single nucleotide polymorphism of chemokine CX3C receptor 1 (CX3CR1) gene and acute coronary syndrome (ACS). Methods 951 cases of Han population in northern China were collected continuously, of which 520 cases were male, 431 cases were female, and the age was 35-75 years old. According to the results of coronary angiography (CAG), the selected subjects were divided into two groups:(1)case group (n＝512):ACS patients; (2)control group (n＝439):non coronary heart disease patients. The case group was divided into three subgroups according to the number of vascular lesions that were examined by CAG. The genotypes of rs3732378 single nucleotide polymorphisms of CX3CR1 gene were determined by sequencing. Multiple factor Logistic regression was used to analyze the relationship between the CX3CR1 gene rs3732378 polymorphism and the risk of ACS. The expression of chemokine CX3C ligand 1 (CX3CL1) in plasma was detected by enzyme-linked immunosorbent assay. Results There was no significant difference in the distribution frequency of rs3732378 genotypes and alleles of CX3CR1 gene in the two groups (P＞0.05). The overall and stratified analysis of rs3732378 polymorphisms and ACS risk showed that three genotypes TT, TC and CC of CX3CR1 rs3732378 polymorphisms did not increase the risk of ACS (P＞0.05). Subgroup analysis showed that the genotype and allele of rs3732378 polymorphic loci were not related to the number of coronary artery lesion (χ²＝0.135, P＝0.998; χ²＝0.026, P＝0.987). There was no significant difference in the expression level of CX3CL1 among three rs3732378 genotypes in the case group and the control group (P＞0.05). Conclusion The rs3732378 polymorphism of CX3CR1 gene is not a susceptible gene of ACS, and rs3732378 polymorphism does not increase the risk of ACS in the Han population of northern China.