Abstract: In this study, the fusion proteins including two copies of T-cell epitope(aa21-40) and B-cell epitope(aa141-160) of VP1 of food-and-mouth disease virus typed O and labile enterotoxin B subunit (LTB) and/not stable enterotoxinⅠ (STI) of Escherichia coli were analyzed as candidate vaccine against FMDV and E.coli. The proteins 2020-2020VP1,2020-B-2020 and 2020-B-2020-STI were used to vaccinate guinea pigs, rabbits and 6-8 weeks old BALB/c mice, then the immune responses were observed. The fusion proteins could induce proliferation of spleen T cells in vaccinated guinea pigs, and could elicit FMDV neutralizing antibody. It could be concluded that the three fusion proteins could activate FMDVspecial cellular and humoral immune-response simultaneously. At the same time, the fusion proteins 2020-B-2020 and 2020-B-2020-STI could protect mice from challenge of enterotoxigenic E. coli C83902 and the protecting-rate were 60%/1.5 MLD and 100%/1.5 MLD respectively. The fusion protein including STI enterotoxin could induce neutralizing antibody for STI toxin in rabbits, moreover, the fusion protein had no STI toxicity. The fusion proteins 2020-B-2020 and 2020-B-2020-STI could be recognized specially by CTB antibody in ELISA. So that, it can be concluded that the fusion protein 2020-B-2020-STI is potent to be efficient FMDV and ETEC vaccine.