Aim To investigate the correlation between milk fat globule epidermal growth factor 8 (MFG-E8) gene single nucleotide polymorphism and coronary heart disease (CHD) in Han people in northern Guangxi. MethodsA total of 158 CHD patients of Han nationality in northern Guangxi were selected as CHD group, and 183 age-and gender-matched healthy subjects were selected as control group. Serum MFG-E8 levels in CHD group and control group were detected by enzyme-linked immunosorbent assay. Genotypes of MFG-E8 gene rs1878326 and rs4945 loci were detected by restriction fragment length polymorphism polymerase chain reaction and DNA direct sequencing. At the same time, the relationship between the genotypes of related loci and serum MFG-E8 levels was analyzed in CHD group. Results The serum MFG-E8 level in CHD group was 1.63 (1.1,2.04) μg/L, and that in control group was 3.29 (2.9,3.59) μg/L.The serum MFG-E8 level in CHD group was significantly lower than that in control group (Z＝－15.370, P＜0.001). The frequency of CA genotype at rs4945 C＞A locus of MFG-E8 gene in CHD group was 31.6%, and the frequency of A allele was 15.8%, which were higher than those in control group (18.6%, 9.3%), and the difference was statistically significant (P＜0.05). rs4945 C＞A locus CA genotype had higher risk of CHD than CC genotype (OR＝2.9,5%CI:1.229～3.349), and A allele had higher risk of CHD than C allele (OR＝1.5,5%CI:1.153～2.921). There was no significant difference in serum MFG-E8 levels between different genotypes at rs4945 C＞A locus in CHD group (Z＝－1.580, P＝0.114). There was no correlation between the genotype and allele frequency of rs1878326 C＞A locus and CHD (P＞0.05). Conclusion The serum MFG-E8 level of CHD patients of Han nationality in northern Guangxi is significantly lower than that of normal people, and the rs4945 C＞A polymorphism of MFG-E8 gene is associated with CHD.