Flexible　metal–organic　framework　(MOF)　films　are　greatly　desired　for　the　separation　of　hazardous　molecules　and　ions　from　wastewater.　The　current　MOF　films　are　usually　horizontally　deposited　on　the　substrates,　and　thus　restricted　by　brittleness,　low　exposure　of　surface　area,　as　well　as　poor　separation　functions.　Here,　an　organic–inorganic　mixed　substrate　is　firstly　fabricated　by　growing　hydroxyapatite　(HA)　nanowire　arrays　on　the　cellulose　fiber　(CF).　Subsequently,　MIL-100(Fe)　nanocrystals　are　assembled　on　the　surfaces　of　HA　nanowire　arrays　through　a　layer-by-layer　manner,　leading　to　a　unique　vertical　MOF　film.　The　resulting　vertical　MOF　films　show　competitive　advantages　over　the　horizontal　counterparts:　(i)　they　show　excellent　flexibility　and　they　are　tolerant　to　serious　physical　damage;　(ii)　they　have　multiple　separation　functions　including　ion　exchange　of　HA,　excellent　adsorption　of　MOFs,　and　strong　electrostatic　interaction　of　CF;　and　(iii)　the　agglomeration　of　MIL-100(Fe)　nanocrystals　is　effectively　suppressed.　Therefore,　the　average　roughness,　specific　surface　area,　and　average　pore　size　of　films　are　optimized.　As　a　result,　the　vertical　MOF　films　show　universal　separation　of　positively/negatively-charged　dyes　and　Pb2+　ion,　with　high　removal　rates　of　＞　94　%.　More　appealing,　the　mixed　pollutants　in　the　complex　wastewater　can　be　one-step　separated　through　the　vertical　MOF　films,　with　high　removal　rates　of　＞　96　%.　©　2023　Elsevier　B.V.