Tumor-associated inflammation and aberrantly expressed biomarkers have been demonstrated to play crucial roles in the cancer microenvironment. Cyclooxygenase-2 (COX-2), a prominent inflammatory factor, is highly expressed in tumor cells and contributes to tumor growth, recurrence and metastasis. Overexpression of COX-2 may occur at both transcriptional and post-transcriptional levels. Thus, an improved understanding of the regulatory mechanisms of COX-2 can facilitate the development of novel antitumor therapies. MicroRNAs (miRNAs) are a group of small non-coding RNAs that act as translation repressors of target mRNAs, and play vital roles in regulating cancer development and progression. The present review discusses the association between miRNAs and COX-2 expression in different types of cancer. Understanding the regulatory role of miRNAs in COX-2 post-transcription can provide novel insight for suppressing COX-2 expression via gene silencing mechanisms, which offer new perspectives and future directions for the development of novel COX-2 selective inhibitors based on miRNAs. Contents 1. Introduction 2. Roles of COX-2 in cancer 3. Expression of miRNAs in cancer 4. Post-transcriptional COX-2 regulation is mediated by miRNAs 5. Upregulated expression of miRNAs by COX-2 selective inhibitor 6. Conclusions