We made a case-control study to investigate a possible association between ALOX5AP-SG13S114A/T, COX-2-765G/C, and COX-1-50C/T polymorphisms with cerebral infarction in a Chinese population. A total of 411 cases with cerebral infarction were included; 411 controls matched for age, gender, and risk factors were also selected. The ALOX5AP-SG13S114A/T (rs10507391), COX-2-765G/C (rs20417), and COX-1-50C/T (rs3842787) polymorphisms were determined using PCR-RFLP. The generalized multifactor dimensionality reduction method was employed to detect gene-gene interactions. Based on single-gene analysis, there were no significant differences in the genotype and allele frequency distributions of ALOX5AP-SG13S114A/T, COX-2-765G/C, and COX-1-50C/T between the cerebral infarction group and controls. However, in those cases carrying ALOX5AP-SG13S114AA as well as COX-2-765CC, the risk of cerebral infarction increased significantly by 2.84 times (95%CI = 1.324-6.543). The single-gene ALOX5AP-SG13S114A/T, COX-2-765G/C, and COX-1-50C/T polymorphisms appear not to be associated with the development of cerebral infarction in Chinese populations. However, the interaction between ALOX5AP-SG13S114AA and COX-2-765CC apparently increases susceptibility to cerebral infarction.