Aim To explore the association between mammalian target of rapamycin (mTOR) gene polymorphism and genetic susceptibility to coronary heart disease in Han population in South China, and provide new ideas for early prevention and intervention of coronary heart disease. Methods Polymerase chain reaction-ligase detection reaction (PCR-LDR) technology was used to classify mTOR gene polymorphisms in 804 patients with coronary heart disease and 979 control subjects. The genotypes of rs2295079 and rs1883965 of mTOR gene were detected. The association between each polymorphic site and susceptibility to coronary heart disease was analyzed by unconditional Logistic regression. Results There was no statistical difference in the distribution of alleles and genotype frequencies of rs2295079 and rs1883965 between the coronary heart disease group and the control group (P＞0.05); the distribution frequencies of the haplotype rs2295079C-rs1883965A constructed by these two loci in the coronary heart disease group and the control group were 8.3% and 6.5%, respectively, and the coronary heart disease group was significantly higher than the control group; individuals carrying rs2295079C-rs1883965A haplotype had a significantly increased risk of developing coronary heart disease (OR＝1.29, P＝0.047), this haplotype had a more significant risk of developing coronary heart disease in people aged ≤60 years old (OR＝1.73, P＝0.009). Conclusion The haplotype rs2295079C-rs1883965A of the mTOR gene is closely related to the genetic susceptibility to coronary heart disease, and is more obvious in the population aged ≤60 years old, suggesting that this haplotype may be an important rick factor in increasing the risk of coronary heart disease in the Han population in South China.