AbstractLaccase, an enzyme capable of degrading lignin, has become an effective agent for green processing and has great significance for the protection of the environment and the development of a low-carbon economy. In this work, wood fibers were selected as the raw material, and with activation by a laccase-mediator system, lignin was changed to a natural adhesive material, and the high temperature/high pressure method was used to prepare medium density fiberboard (MDF). The bonding mechanism was explored with measurements of Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), environmental scanning electron microscope (ESEM), and X-ray diffraction (XRD). It was found that the self-adhesive effect was realized through esterification, hydrogen bonding, polycondensation, coupling, and a Schiff base reaction, among which coupling and polycondensation were the primary reactions. The chemical bonds between the MDF interior and surface varied because of the mobility of the lignin during the reaction.