Objective To investigate the relationship between Ghrelinand Gas6 gene polymorphisms and the risk of coronary heart disease. Methods From May 2022 to May 2023, 100 patients with coronary heart disease admitted to our hospital were selected as the study subjects and recorded as the observation group, and another 100 healthy subjects were selected as the control group. Serum Ghrelin and Gas6 levels were determined by enzyme-linked immunosorbent assay. Ghrelin and Gas6 gene polymorphisms were determined by TaqMan-PCR, and the relationship between Ghrelin and Gas6 gene polymorphisms and the risk of coronary heart disease was analyzed. Results Compared with control group, the serum Ghrelin level in observation group was significantly decreased, Gas6 level was significantly increased (P＜0.05); Genotype frequencies of AA, CA and CC were 47.00%, 36.00% and 17.00% in control group, 11.00%, 18.00% and 71.00% in observation group, allele frequencies of C and A were 35.00% and 65.00% in control group, and 80.00% and 20.00% in observation group, respectively. There was statistical significance between groups (P＜0.05). Compared with control group, Ghrelin level in CC genotype was decreased (P＜0.05), but there was no significant difference in AA and CA genotype in observation group (P＞0.05). Three different genotypes of Ghrelin loci were used as independent variables, wild-type homozygotes of each loci were used as reference, and other genotypes were used as dummy variables. Binary Logistic regression model was fitted, and the results showed that CC genotype of Ghrelin gene increased the risk of coronary heart disease (OR=2.967). There was statistical significance between groups (P＜0.05). The frequencies of GG, GA and AA genotypes were 40.00%, 36.00% and 24.00% in the control group, 52.00%, 44.00% and 4.00% in the observation group, and the frequencies of A and G alleles were 42.00% and 58.00% in the control group, 26.00% and 74.00% in the observation group. There was statistical significance between groups (P＜0.05). Compared with the control group, Gas6 level in the observation group was increased in GA genotype (P＜0.05), decreased in AA genotype (P＜0.05), but there was no significant difference in Gas6 level in GG genotype (P＞0.05). Three different genotypes of Gas6 locus were used as independent variables, wild type homozygotes of each locus were used as the basis, and other genotypes were used as dummy variables. Binary Logistic regression model was fitted, and the results showed that Gas6 GA genotype increased the risk of coronary heart disease (OR=2.157). AA genotype decreased the risk of coronary heart disease (OR=0.523), which was statistically significant between groups (P＜0.05). Conclusion Ghrelin and Gas6 levels are closely related to coronary heart disease. Ghrelin and Gas6 gene polymorphisms are associated with the risk of coronary heart disease, and may be involved in the pathogenesis of coronary heart disease