PTGS2 genetic 3′ untranslated region (3′UTR) miRNA binding sites variants are significantly associated with cancer risk; however, the roles of genetic variants in PTGS2 gene 3′UTR and post-transcriptional regulation have not been elucidated. We report that rs689470 and rs5275 in the PTGS2 3′UTR have potential miRNA-binding sites by using bioinformatics analysis. However, only the rs689470 was significantly associated with PTGS2 mRNA expression in lymphoblastoid cell lines (P = 0.026), but not for rs5275 (P = 0.626). rs689470 might be putative variants mediating the post-transcriptional regulation of target PTGS2 gene. Better understanding of how 3′UTR variants regulate PTGS2 activity will pave the way to targeting the PTGS2 pathway in cancer therapy.