A　facile　strategy　for　highly　efficient　fabrication　of　chiral　monolithic　column　was　carried　out　by　the　simple　＇one-pot＇　hydroxymethyl　polycondensation　of　native　β-cyclodextrin　(β-CD)　and　urea-formaldehyde　(UF).　In-situ　rapid　substitution　of　native　β-CD　and　efficient　polycondensation　of　β-CD　products　and　UF　oligomers　was　proposed　and　fulfilled　in　one　pot.　The　feasibility,　mechanism　and　key　parameters　of　polycondensation　reaction　were　discussed.　The　data　on　crosslinking　polycondensation　and　reaction　kinetics　were　further　evaluated.　Characteristics　including　the　morphologies,　permeability　and　structure　stability　of　the　resultant　monolithic　columns　were　also　studied.　Under　the　optimal　conditions,　the　＇one-pot＇　hydroxymethyl　polycondensation　was　accomplished　in　an　aqueous　solution　within　only　10　mins.　Satisfactory　stability　and　repeatability　were　gained,　and　good　enantioseparation　of　eight　model　enantiomers　was　successfully　achieved　with　the　resultant　β-CD-based　monolith.　It　was　simple　and　highly　efficient,　and　the　organic　solvents,　special　CD　derivatives　and　tediously　long-time　polymerization　reaction　were　successfully　avoided,　which　might　light　a　new　access　to　rapid　preparation　of　CD-chiral　monolith　for　high-performance　enantioseparation.　©　2019