In　the　face　of　the　mass　production　and　consumption　of　chloroquine　(CLQ),　the　presence　of　CLQ　has　posed　a　significant　threat　to　the　water　environment　and　living　organisms　due　to　its　bio-accumulative　and　persistent　nature.　In　this　work,　a　heterogeneous　electro-Fenton　system　using　a　pyrite-modified　carbon　felt　as　the　cathode　(EF-FeS2-CF)　was　constructed　to　remove　CLQ.　EF-FeS2-CF　was　found　to　achieve　92.4　±　0.1%　removal　of　5　mg/L　CLQ　after　30　min　at　20　mA　and　exhibited　an　outstanding　catalytic　performance　for　CLQ　removal　in　wide　ranges　of　operating　conditions,　excellent　recyclability　with　low　iron　leaching　(＞90%　30-min　CLQ　removal　efficiency　for　all　five　cyclic　experiments　which　led　to　only　an　accumulative　Fe　loss　of　＜0.3%)　and　remarkable　application　potential　in　different　aqueous　environments　without　any　pH　adjustment.　Both　O2•-　and　•OH　were　found　to　greatly　contribute　to　CLQ　degradation　while　the　latter　played　a　major　role　(＞50%　CLQ　removal).　To　describe　CLQ　degradation　towards　complete　mineralization　in　EF-FeS2-CF,　three　CLQ　degradation　paths　were　proposed　based　on　the　main　degradation　intermediates　identified　with　generally　lower　ecotoxicities.　Such　an　EF-FeS2-CF　system　therefore　presents　promising　application　potential　to　treat　CLQ-laden　waters.　©　2024　Elsevier　Ltd