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Extracellular matrix metalloproteinase inducer (EMMPRIN) had been reported to be involved in the occurrence and development of coronary heart disease (CHD) in previous studies. This study aimed to investigate whether single nucleotide polymorphisms of EMMPRIN and matrix metalloproteinase-9 (MMP-9) contributed to the onset and severity of CHD. One thousand seventy patients suspected to have CHD were enrolled into the study. Each patient had undergone coronary angiogram, and the severity of coronary artery stenosis was assessed by Gensini score. Eight hundred twelve patients were confirmed to have CHD, while 258 patients were selected as non-CHD control. All patients were genotyped for five EMMPRIN polymorphisms (rs8259, rs28915400, rs4919859, rs6758, and rs8637) and one MMP-9 polymorphism (rs3918242) by polymerase chain reaction-restriction fragment length polymorphism and confirmed by direct sequencing. EMMPRIN polymorphism rs8259 and MMP-9 polymorphism rs3918242 were found to be associated with CHD (rs8259: AT vs. AA, adjusted odds ratio [OR] = 2.038, adjusted 95% confidence interval [CI] = 1.080-3.847, p  = 0.028; rs3918242: CT vs. CC, adjusted OR = 0.607, adjusted 95% CI = 0.403-0.916, p  = 0.017, TT vs. CC, adjusted OR = 2.559, adjusted 95% CI = 1.326-4.975, p  = 0.006). No crossover effects were observed although a single environmental or genetic factor had an impact on the occurrence of CHD. The value of the Gensini score revealed that severity of CHD decreased in the rs3918242 CT carriers in both the male and female population. Our study suggested that EMMPRIN rs8259 and MMP-9 rs3918242 polymorphisms may contribute to pathological process of CHD. It could play a critical role in the prediction of CHD.