Inflammatory processes are essential for innate immunity and contribute to carcinogenesis in various malignancies, such as colorectal cancer, esophageal cancer and lung cancer. Pharmacotherapies targeting inflammation have the potential to reduce the risk of carcinogenesis and improve therapeutic efficacy of existing anti-cancer treatment. Non-steroidal anti-inflammatory drugs (NSAIDs), comprising a variety of structurally different chemicals that can inhibit cyclooxygenase (COX) enzymes and other COX-independent pathways, are originally used to treat inflammatory diseases, but their preventive and therapeutic potential for cancers have also attracted researchers' attention. Pharmacogenomic variability, including distinct genetic characteristics among different patients, can significantly affect pharmacokinetics and effectiveness of NSAIDs, which might determine the preventive or therapeutic success for cancer patients. Hence, a more comprehensive understanding in pharmacogenomic characteristics of NSAIDs and cancer-related inflammation would provide new insights into this appealing strategy. In this review, the up-to-date advances in clinical and experimental researches targeting cancer-related inflammation with NSAIDs are presented, and the potential of pharmacogenomics are discussed as well.Copyright © 2022 Lai, Liu, Wu, Cai, Jie, Xu and Deng.