Early mortality syndrome (EMS) or acute hepatopancreatic necrosis disease (AHPND), results in significant mortality in penaeid shrimp aquaculture. AHPND is caused by toxins secreted by pathogenic strains of Vibrio parahaemolyticus, that have acquired a unique 63–70 kb AHPND-associated plasmid (pVA1). This plasmid encodes the binary PirA/BVP toxins that consist of two subunits PirAVP and PirBVP. Consequently, the degradation of these toxins might be a valid strategy to control or mitigate AHPND. There is literature-based evidence that the application of Bacillus improves shrimp survival upon challenge with pathogenic V. parahaemolyticus. In this study, Bacillus subtilis DSM33018 strain was shown to degrade AHPND toxins in vitro, as detected by Western blots. Further, an in vivo challenge test, using gnotobiotically cultured brine shrimp Artemia franciscana exposed to PirA/BVP toxins, the DSM33018 Bacillus strain could completely alleviate toxicity. This finding indicates that mitigation of AHPND might include Bacillus-based degradation of PirVP toxins. •This is the first scientific evidence on AHPND toxin degradation by Bacillus strains.•PirBVP is more susceptible to degradation by Bacillus strains than PirAVP.•PirA/BVP-induced mortality in Artemia can be mitigated by certain Bacillus strains