The　performance　of　thiosulfate-driven　denitrification　(TDD)　granule　reactor　and　the　mechanism　of　granule　sludge　bulking　were　investigated　in　this　study.　The　results　showed　that　TDD　granule　bulking　occurred　under　12　kgNm-3d-1　of　nitrogen　loading　rate　(NLR).　The　higher　NLR　promoted　accumulation　of　intermediates　in　the　carbon　fixation　pathway,　including　citrate,　oxaloacetate,　oxoglutarate　and　fumarate.　The　carbon　fixation　improved　amino　acids　biosynthesis,　which　increased　proteins　(PN)　in　extracellular　polymers　(EPS)　to　134.6　&　PLUSMN;　11.8　mg/gVSS.　The　ex-cessive　PN　altered　the　content,　components　and　chemical　groups　of　EPS,　leading　to　change　of　granule　structure　and　decline　in　settling　property,　permeability　and　nitrogen　removal.　By　adopting　the　strategy　of　intermittently　reducing　NLR,　excess　amino　acids　in　sulfur-oxidizing　bacteria　was　consumed　through　microbial　growth-related　metabolism　in-stead　of　EPS　synthesis.　Therefore,　the　nitrogen　removal　rate　increased　to　10.23　kg-Nm-3d-1　and　maintained　stable　in　the　long　term.　The　EPS　contents　decreased　from　168.8　&　PLUSMN;　13.5　mg/gVSS　to　93　&　PLUSMN;　11.5　mg/gVSS　and　the　SVI5　decreased　from　66　&　PLUSMN;　3.5　ml/g　to　25　&　PLUSMN;　1.5　ml/g.　These　findings　provide　an　effective　strategy　to　prevent　granule　bulking　and　guide　practical　application　of　TDD　process.