Aims: To observe the influence of the peroxisome proliferator-activator receptor-G (PPAR-G) gene and cytochrome P4501A1 (CYP1A1) single-nucleotide polymorphisms (SNPs), and interactions among several SNPs on coronary artery disease (CAD) risk. Methods: A total of 1106 participants (including 583 males and 523 females) including 550 CAD patients and 556 control subjects were recruited in this study, and the mean age for these participants was 55.5 +/- 11.8 years old. Logistic regression was used to observe association of SNP within PPARG and CYP1A1 with CAD risk and GMDR model was used to screen the best interaction combinations. Results: CAD susceptibility was higher in those with homozygous mutant of rs10865710, rs1805192 and rs4646903 than those with wild-type homozygotes, OR (95% CI) were 1.47 (1.15-1.92), 1.69 (1.27-2.09) and 1.72 (1.35-2.32), respectively. We also found a significant two-locus model involving rs1805192 and rs4646903 (p = 0.0107), and the cross-validation consistency of this locus model was 10 of 10, the testing accuracy of this model is 62.17%. Logistic regression shown that CAD risk was the highest in those with rs1805192-Pro/AlaorAla/Ala and rs4646903-AG+GG genotype, and was lowest in those with rs1805192-Pro/ Pro and rs4646903- AA genotype, OR(95% CI) = 3.56 (1.91-5.42). Conclusions: Polymorphism in rs10865710, rs1805192 and rs4646903 and interaction between rs1805192 and rs4646903 were related with increased CAD susceptibility.