The invention discloses a beta-caryophyllene derivative as well as a preparation method and application thereof. The structural general formula of the beta-caryophyllene derivative provided by the invention is shown by a formula I, wherein R is selected from any one of the following groups: a hydroxy group, an amino group, an ester group and an amide group. The inventor of the invention has verified through experiments that a reaction factor has good reactivity, stability, easily available raw materials and a certain reaction rate at the same time. The application of this reaction factor is proved in corresponding protein labeling and cell labeling experiments, which provides a new idea for the development of related biorthogonal reaction factors.