A novel calix[4] open-chain crown ether (p-tert-butylcalix[4]arene-1,3-bis(allyloxyethy) ether)modified, organic-inorganic hybrid silica-based monolithic column possessing vinyl ligands for CEC is described. The monolithic silica matrix containing a vinyl functionality was synthesized by in situ cocondensation of tetramethoxysilane (TMOS) and vinyl-trimethoxysilane (VTMS) via sol-gel process and chemically modified with calix[41 open-chain crown ether by free radical polymerization procedure using =alpha, alpha'-azobisisobutyronitrile (AIBN) as an initiator. Morphology of the monolithic column was examined by SEM and the successful incorporation of calix[41 open-chain crown ether to the vinyl-hybrid monolith was characterized by infrared (IR) spectra. Compared with an unmodified vinyl-hybrid monolithic column, slightly stronger EOF at pH > 7.5 was observed for this monolithic column due to the ionization of phenolic hydroxyls on the lower rim of calix[4]arene. VTMS/TMOS ratios in the reaction mixture were varied and 1:4 was found to be optimum to obtain homogeneous monolith with good permeability. The performance of the column was evaluated by nucleotides, beta-blockers, neurotransmitters, and PAHs as test solutes and compared with that of unmodified vinyl-hybrid monolithic column. Greatly improved column performance was obtained due to the host-guest interaction and intermolecular hydrogen bonding provided by the calix[4] open-chain crown ether moiety. The column efficiencies for neurotransmitters and nucleotides are up to 120 000 and 110 000 plates/m, respectively. Migration time and theoretical plate number reproducibilities were reasonable with RSDs less than 1.0 and 1.8% each for within column runs and not more than 7.2 and 8.6% each for column-to-column measurements, using four nucleotides as test solutes.