In this study, three cooking methods of boiled, fried and braised shrimps were used to treat the meat of Litopenaeus vannamei, and the cooked shrimp was subjected to in vitro simulated saliva-gastric-intestinal digestion to investigate the immunological activity after cooking. Changes of major allergen tropomyosin in shrimp were analyzed by SDS-PAGE, Western-blotting and indirect ELISA. The results of SDS-PAGE showed that there was no significant change in the TM bands by three cooking methods, indicating that the TM did not undergo degradation during cooking; the results of immunoblotting and indirect ELISA showed that the immunological activity of TM in boiled, fried and braised shrimp lost 2.08%, 11.33% and 15.56%, respectively. However, the immunological activity of the in vitro simulated digestion products of shrimp meat after cooking was significantly lost, and the immunological activitiy of boiled, fried and braised shrimp were decreased by 86.90%, 88.94% and 97.39%, respectively. Studies have shown that the reduction of shrimp TM immunological activity mainly occurs in the simulated intestinal fluid digestion stage, three cooking treatments can reduce the immunological activity of TM, and the braising treatment significantly reduced the immunological activity of TM. This experiment provides a theoretical basis for the study of allergen reduction mechanism and the development of hypoallergenic aquatic products.