We conducted a case-control study to investigate the genetic variants Interleukin-1β(IL-1β) +3953 C/T (rs1143634), IL-6 -174G/C (rs1800795), IL-8 -251T/A (rs4073), and IL-10 -1082A/G (rs1800896) and -819C/T (rs1800871) in the development of coronary artery disease (CAD). A total of 410 individuals with CAD were enrolled between January 2012 and December 2014. Genotyping of the five gene polymorphisms was performed using the polymerase chain reaction combined with restriction fragment length polymorphism methodology. By multivariate logistic regression analysis, we found that the frequencies of the CC genotype and the C allele of IL-6 -174G/C were significantly correlated with a higher risk of CAD; the adjusted ORs (95%CIs) were 2.37 (1.37-4.14) and 1.49 (1.19-1.86), respectively. In addition, the AG and GG genotypes and the G allele of IL-10 -1082A/G were also significantly associated with a higher risk of CAD, and the ORs (95%CIs) were 1.42 (1.04-1.95), 2.16 (1.42-3.30), and 1.56 (1.27-1.93), respectively. However, IL-1β+3953 C/T, IL-8 -251T/A, and IL-10 -819C/T did not significantly correlate with CAD risk. Our study suggests that the IL-6 -174G/C (rs1800795) and IL-10 -1082A/G (rs1800896) polymorphisms might be involved in the pathogenesis of CAD, and likely contribute to the genetic susceptibility for CAD.