Cryptocaryon irritans is an important parasite in mariculture fish, which can infect almost all kinds of marine bony fishes, causing fatal diseases and huge economic losses to marine aquaculture in China. Due to the property of living in the epidermis of the skin and gills, this makes it as good model to study the mucosal immunity of seawater fish, which are conducive to developing effective vaccine. In this paper, we reviewed the current progress of grouper (Epinephelus coioides) anti-C. irrians infection, which will provide the theoretical support for carrying out the immune prevention and control measures against C. irritans. The existing results show that after C. irritans infection, grouper skin mucous or its culture supernatant can immobilize the theronts, and specific IgM antibody anti-C. irritans was detected, which is produced by the antibody secreting cells in the skin and plays an important role in resistance to parasitic infections; We found many immune cells such as NCC cells, neutrophil cells around the parasites; meanwhile, the expression levels of some chemokines and chemokine receptors were significantly increased in the infection sites, implying that these immune cells may also involve resistance to parasite infection; In addition, we found that rabbitfish (Siganus oramin) was naturally resistant to C. irritans infection, the serum and skin mucous of which could kill the theronts and tomont of C. irritans. Next, a novel protein that is lethal to C. irritans was isolated from the serum of rabbitfish and which was identified as L-amino acid oxidase. Finally, by immune experiment, we proved the feasibility of vaccines for prevention and control of cryptocaryoniasis.