Quaternary　ammonium　compounds　(QACs)　are　recommended　disinfectants　with　surfactant　properties,　surpassing　triclosan　(TCS)　and　chloroxylenol　(PCMX).　Given　the　transition　from　traditional　disinfectants,　it　is　essential　to　investigate　their　impacts　on　biological　nitrogen　removal　systems　and　the　fate　of　resistance　genes　(RGs).　In　this　study,　three　biofilm-based　partial　nitrification-anammox　(PN/A)　systems　were　established.　A　reactor　named　PD　was　successively　exposed　to　1　mg/L　PCMX　and　3　mg/L　dioctadecyldimethylammonium　chloride　(DODMAC,　a　common　QACs).　A　reactor　named　TD　was　successively　exposed　to　1　mg/L　TCS　and　3　mg/L　DODMAC.　A　reactor　named　CD　served　as　a　control　with　only　3　mg/L　DODMAC　exposure.　Results　indicated　that　the　total　nitrogen　removal　performance　of　CD　deteriorated　markedly　with　DODMAC　exposure　compared　to　that　of　PD　and　TD.　This　phenomenon　correlated　closely　with　variations　in　RGs　and　their　co-selection　patterns.　Pre-exposure　to　PCMX　or　TCS　increased　the　abundance　of　RGs　in　the　extracellular　DNA　of　the　PN/A　biofilm,　but　reduced　RGs　abundances　in　the　extracellular　DNA　of　water.　The　tolerance　of　the　PN/A　system　to　successive　exposure　to　the　two　disinfectants　may　be　strengthened　through　co-selection　of　QACs　RGs　(qacEdelta1–01,　qacEdelta1–02,　qacH-01　and　qacH-02)　and　mobile　genetic　elements　(intI1　and　tnpA-04).　Furthermore,　potential　hosts　of　RGs　are　crucial　for　maintaining　PN/A　performance.　Accumulation　of　extracellular　polymeric　substances,　reactive　oxygen　species,　and　lactate　dehydrogenase　plays　vital　roles　in　the　accumulation　and　transmission　of　RGs　within　the　PN/A　system.　©　2023　Elsevier　Ltd