This protocol describes a method to site-speci cally cleave proteins using chemicals upon insertion of the appropriate tag into the cleaving proteins.It can be applied to water soluble as well as membrane proteins with e ciency comparable to enzymes.The fact that chemicals can be used to replace enzymes in this method highlights the unique aspects of this technology.The cleavage can be achieved within a day upon obtaining target proteins.Detailed technical aspects of this method will be discussed in this protocol.