In order to control aquaculture diseases and understand the influence of pathogen microorganisms on cephalopoda culture, we selected vibrio with high incidence in seawater culture, including V.anguillarum and V.parahemolyticus, to study their virulence level and pathogenic mechanism against shortarm octopus. Through direct injection of diluted bacteria solution into shortarm octopus carpus arm, the death rate and half lethal time of shortarm octopus after infection were observed, as well as the effects of various bacteria on the structures of shortarm octopus liver, gill, gill heart and white body. The results showed that V.anguillarum and V.parahemolyticus were both highly pathogenic to shortarm octopus, reaching a semi-fatality rate at 60 h and 48 h, respectively. In addition, the activity of octopus was decreased, weakness and abdominal swelling were observed; Through the observation of paraffin sections and HE staining and ultramicroscopic structure of diseased and healthy tissues, it was found that the liver, gill, gill heart and white body of the diseased octopus showed different degrees of tissue or cell structure damage. The above results indicated that both V.anguillarum and V.parahemolyticus were significantly pathogenic to shortarm octopus, and the pathogenicity of V.parahaemolyticus might be stronger, which would be one of the greatest threats of shortarm octopus large-scale farming if the conditions were suitable.