Antibiotics　and　quaternary　ammonium　compounds　(QACs)　usually　co-exist　in　wastewater　treatment　plants.　Hence,　three　sequencing　batch　reactors　were　established　and　named　as　R1,　R2　and　R3,　to　investigate　the　effects　of　individual　and　combined　exposure　of　different　concentrations　of　ciprofloxacin　(CIP)　(0.2,　1.0　and　2.0　mg/L)　and　dialkyldimethyl　ammonium　compound　(DADMAC)　(0.4,　2.0　and　4.0　mg/L)　on　the　performance,　microbial　community　structures　and　resistance　genes　(RGs)　in　nitrifying　system　during　150　days.　Results　showed　that　CIP　had　a　slight　effect　on　ammonia　oxidation　activity,　while　2.0　and　4.0　mg/L　DADAMAC　could　obviously　inhibit　it,　and　the　combination　of　CIP　and　DADMAC　had　a　synergistic　inhibitory　effect.　Besides,　both　CIP　and　DADMAC　caused　partial　nitrification,　and　the　order　of　nitrite　accumulation　rate　was　ranked　as　R3　＞　R2　＞　R1.　The　combination　of　CIP　and　DADMAC　had　an　antagonistic　effect　on　the　increase　of　sludge　particle　size　and　α-Helix/(β-Sheet　+　Random　coil)　was　lowest　in　R3　(0.40).　The　combination　of　CIP　and　DADMAC　synergistically　stimulated　most　intracellular　RGs　in　sludge,　and　the　relative　abundances　of　target　RGs　(e.g.,　qacEdelta1-01,　qacH-01　and　qnrS)　at　the　end　of　operation　in　R3　were　increased　by　4.61–18.19　folds　compared　with　those　in　CK,　which　were　1.34–5.57　folds　higher　than　the　R1　and　R2.　Moreover,　the　combination　of　CIP　and　DADMAC　also　promoted　the　transfer　of　RGs　from　sludge　to　water　and　enriched　more　potential　hosts　of　RGs,　further　promoting　the　spread　of　RGs　in　nitrifying　system.　Thus,　the　combined　pollution　of　CIP　and　DADMAC　in　wastewaters　should　attract　more　attentions.　©　2024　Elsevier　B.V.