An　organic-silica　hybrid　monolith　was　prepared　by　a　single-step　ring-opening　polymerization　of　octaglycidyldimethylsilyl　polyhedral　oligomeric　silsesquioxane　(POSS-epoxy),　polyethylenimine　(PEI),　and　β-cyclodextrin　(β-CD)　in　a　ternary　porogenic　solvent　consisting　of　polyethylene　glycol,　1,4-butanediol,　and　1-propanol.　The　framework　of　POSS-PEI　hybrid　monolith　could　offer　well-defined　3D　skeleton,　while　β-CD　with　the　ability　of　forming　a　host-guest　inclusion　complexes　with　a　variety　of　compounds　could　show　an　ability　of　specific　selection.　The　obtained　hybrid　monoliths　were　successfully　applied　for　separation　of　phenols,　benzoic　acids,　and　nucleobases.　Especially　due　to　the　introduction　of　β-CD,　positional　isomers　including　hydroquinone　and　resorcinol,　o-nitrophenol　and　p-nitrophenol,　as　well　as　p-chlorophenol　and　o-chlorophenol　were　baseline　separated　and　the　column　efficiency　reached　82 300　plates/m　for　hydroquinone.　©　2018　WILEY-VCH　Verlag　GmbH　&　Co.　KGaA,　Weinheim