This article summarized the DNA genetic modification and RNA regulation mechanism of Alu elements in tumor development, and discuss the latest clinical applications, so as to put forward advices for subsequent studies and summarize new ideas for tumorigenesis and further gene therapy. Alu elements are abundant repetitive sequence, which account for 10% of the human genome. Genetic modification of tumorigenesis by Alu elements is mainly reflected in insertion, recombination, methylation at the DNA level, and the following events like splicing, exonisation or polyadenylation. Alu RNA also plays an essential regulatory role in tumorigenesis. Free Alu RNA can act as a transduction medium for inflammatory factor-related signaling pathways, while embedded Alu RNA in the 3′ UTRs of mRNA regulates long non-coding RNA, microRNA or circular RNA. In addition to research on mechanisms, Alu elements, especially Alu DNA concentration and integrity is widely used for tumor diagnosis, therapeutic effect monitoring and prognosis prediction. Despite this, there are some challenges in clinical application including standardization, innovation in detection technology and so on. (By Yun Jiang, https://jmg.bmj.com/content/early/2019/03/09/jmedgenet-2018-105761 )