Global　climate　change　intensifies　the　water　cycle　and　makes　freshest　waters　become　fresher　and　vice-versa.　But　how　this　change　impacts　phytoplankton　in　coastal,　particularly　harmful　algal　blooms　(HABs),　remains　poorly　understood.　Here,　we　monitored　a　coastal　bay　for　a　decade　and　found　a　significant　correlation　between　salinity　decline　and　the　increase　of　Karenia　mikimotoi　blooms.　To　examine　the　physiological　linkage　between　salinity　decreases　and　K.　mikimotoi　blooms,　we　compare　chemical,　physiological　and　multi-omic　profiles　of　this　species　in　laboratory　cultures　under　high　(33)　and　low　(25)　salinities.　Under　low　salinity,　photosynthetic　efficiency　and　capacity　as　well　as　growth　rate　and　cellular　protein　content　were　significantly　higher　than　that　under　high　salinity.　More　strikingly,　the　omics　data　show　that　low　salinity　activated　the　glyoxylate　shunt　to　bypass　the　decarboxylation　reaction　in　the　tricarboxylic　acid　cycle,　hence　redirecting　carbon　from　CO2　release　to　biosynthesis.　Furthermore,　the　enhanced　glyoxylate　cycle　could　promote　hydrogen　peroxide　metabolism,　consistent　with　the　detected　decrease　in　reactive　oxygen　species.　These　findings　suggest　that　salinity　declines　can　reprogram　metabolism　to　enhance　cell　proliferation,　thus　promoting　bloom　formation　in　HAB　species　like　K.　mikimotoi,　which　has　important　ecological　implications　for　future　climate-driven　salinity　declines　in　the　coastal　ocean　with　respect　to　HAB　outbreaks.　©　2024　John　Wiley　&　Sons　Ltd.