The present invention belongs to the technical field of marine anti-fouling materials, and discloses a self-polishing zwitterionic anti-fouling resin having a main chain degradability and the preparation therefor and the use thereof. The self-polishing zwitterionic anti-fouling resin is formed by copolymerizing the following three monomers (in the total mass of the monomers): 1% to 80% of an olefinic reactive monomer, 1% to 80% of a cycloketene acetal monomer, and 1% to 80% of a betaine type precursor. The anti-fouling resin has a main chain degradability and a side chain hydrolyzability, and the transition of a coating from being hydrophobic to being hydrophilic is achieved by the hydrolysis of a surface to produce a super-hydrophilic zwitterionic surface, in order to further enhance the anti-fouling ability of the system. The material not only overcomes the disadvantages of poor mechanical properties and poor solubility in an organic solvent of a zwitterionic material, but can also effectively control the long-term stable release of an anti-fouling agent, so as to achieve a synergistic anti-fouling effect of the anti-fouling agent and an anti-protein. The method of the present invention is simple, has a relatively low cost, and is suitable for industrial production. The material is used in the field of marine anti-fouling coatings.