Provided are multiple-exchange unmarked site-specific integration transgenic system and an application thereof, wherein the transgenic system includes: a first construction body which is a TALEN carrier, wherein the TALEN carrier identifies and cuts friendly site sequences; a second construction body including a left homologous arm, a right homologous arm, a selective marker expression cassette, a first integrase recognition sequence loxp and a first integrase recognition sequence lox2272; a third construction body including a targeted exogenous gene, a second integrase recognition sequence loxp' and a second integrase recognition sequence lox2272'; and a fourth construction body including an integrase gene Cre expression cassette. The transgenic system can simply, fast and efficiently achieve site-specific insertion of a targeted exogenous gene in an animal genome, and prepared transgenic animal cells do not contain any resistant marker gene, the preparation cycle is short, preparation is safe and reliable, and the targeted exogenous gene can stably inherited to a next generation.