The immune microenvironment of primary tumors has been reported to be a prognostic factor. We previously reported that the tumor-infiltrating regulatory T cell (Treg) count was positively correlated with the intratumoral cyclooxygenase-2 (COX-2) expression level and was associated with a poor survival among patients with non-small cell lung cancer (NSCLC). Recently, numerous single nucleotide polymorphisms (SNPs) in the COX-2 gene have been identified, and these SNPs may contribute to differential gene expression and enzyme activity levels. However, whether COX-2 genetic variants influence the functions of COX-2 in NSCLC remains unclear. Eighty NSCLC patients who underwent a complete resection at our institute were enrolled. We extracted DNA from the peripheral blood and identified five different COX-2 SNPs. The correlations between the COX-2 SNPs and the expression levels of COX-2, Tregs and Ki-67 were studied. The prognostic significance of the COX-2 SNPs was also evaluated. COX-2 SNPs were not correlated with the expression of COX-2. However, for the COX-2 -1195G/A polymorphism, the AA genotype group had a significantly higher Treg score. Furthermore, the AA group had a significantly higher Treg score regardless of the COX-2 expression level. The COX-2 -1195AA genotype group tended to have a shorter disease-free survival period than the GA/GG group. In conclusion, the COX-2 -1195G/A polymorphism influences the infiltration of Tregs into NSCLC, and the COX-2 SNP factor may be a prognostic factor reflecting Treg infiltration in NSCLC.