Alexandriumcauses serious food safety and human death due to paralytic shellfish toxins (PSTs) production. The associated bacteria can affect PSTs production ofAlexandrium. However, the influencing mechanism is still unclear. Here we firstly screened functional associated bacteria for affecting PSTs production ofAlexandrium catenellain Yangtze Estuary and further studied their influence on physiological process and molecular regulation ofA. catenella. Thirteen bacteria strains for affecting PSTs production ofA. catenellawere selected. TheA. catenellastrains co-cultured with different functional associated bacteria all produced more PSTs than axenic strain with antibiotic treatment. Compared with axenicA. catenella, the non-axenicA. catenellaproduced more algal cells, soluble sugar, soluble protein and neutral lipid. By RNA-seq, it was found that non-axenicA. catenellaproduced more upregulated functional genes than axenicA. catenella. The biosynthesis of cofactors and spliceosome were the dominant different pathways between axenic and non-axenicA. catenellastrains. The sxtA expression was closely related with Arginine and proline metabolism, Arginine biosynthesis, Fatty acid biosynthesis, TCA cycle and Glutathione metabolism, which were all downregulated in axenicA. catenella. Meantime, the non-axenicA. catenellaunder nitrogen deprivation produced less PSTs and functional genes than non-axenic strain under common culture condition, indicating the nitrogen significance for PSTs production. The detailed signal molecular released by associated bacteria for regulating PSTs ofA. catenellaneeds to be further studied.