Aspirin (ASP), the first synthetic drug, is widely used as a non steroidal anti-inflammatory drug. It displays a variety of biological activities, such as anti-thrombosis, anti-inflammatory, anti-tumor, etc. A lot of works about the synthesis and related activity evaluation of its derivatives were reported. There are four kinds of derivatization methods: skeleton derivatization, prodrug derivatization, twin derivatization and metal coordination derivatization. According to the different modification sites, skeleton derivatization could be further divided into C(1)-COOH site modification, C(1)-COOH site and C(2)-OAc site simultaneous modification, C(2)-OAc site modification and benzene ring modification. NO-ASP is the main method to prepare antithrombotic derivatives, and metal coordination modification is the main synthesis scheme of anticancer derivatives. The structure modification and bioactivity research of aspirin in recent twenty years and the synthetic routes of 353 aspirin derivatives and the pharmacological activities of some derivatives are described, which provides a reference for the further development of aspirin derivatives.