Surfactants　could　influence　sludge　morphology　and　disinfectants　were　linked　to　antibiotic　resistance　genes　(ARGs).　Thus,　the　response　of　activated　sludge　and　ARGs　to　long-term　quaternary　ammonium　compounds　(QACs)　exposure　required　further　investigation,　which　is　a　popular　surfactant　and　disinfectant.　Here,　three　sequencing　batch　reactors　were　fed　with　5　mg/L　most　frequently　detected　QACs　(dodecyl　trimethyl　ammonium　chloride　(ATMAC　C12),　dodecyl　benzyl　dimethyl　ammonium　chloride　(BAC　C12)　and　didodecyl　dimethyl　ammonium　chloride　(DADMAC　C12))　for　180　d.　The　long-term　inhibitory　effect　on　denitrification　ranked:　DADMAC　C12　＞　BAC　C12　＞　ATMAC　C12.　Besides,　obvious　granular　sludge　promoted　by　the　increase　of　alpha-Helix/(8-Sheet　+　Random　coil)　appeared　in　DADMAC　C12　system.　Moreover,　intracellular　ARGs　increased　when　denitrification　systems　encountered　QACs　acutely　but　decreased　in　systems　chronically　exposed　to　QACs.　Although　replication　and　repair　metabolism　in　ATMAC　C12　system　was　higher,　ATMAC　C12　significantly　promoted　proliferation　of　extracellular　ARGs.　It　was　noteworthy　that　the　propagation　risk　of　extracellular　ARGs　in　sludge　increased　significantly　during　sludge　granulation　process,　and　intracellular　sul2　genes　in　sludge　and　water　both　increased　with　the　granular　diameter　in　DADMAC　C12　system.　The　universal　utilization　of　QACs　may　enhance　antibiotic　resistance　of　bacteria　in　wastewater　treatment　plants,　deserving　more　attention.