Via the facile ring-opening reaction of epoxy groups with quinine, a novel polymer monolith with quaternary ammonium for reversed-phase/strong anion-exchange mixed-mode has been fabricated for pressurized capillary electrochromatography (pCEC). Optimization on the preparation of quinine-modified monoliths has been investigated, and characteristics including morphology, permeability, mechanical stability, reproducibility, and column performance have been also studied. Active quaternary ammonium groups were conveniently produced to generate cationic action sites and stable anodic electroosmotic flow. Multiple interactions including reversed-phase, strong anion-exchange, electrostatic repulsion and - stacking interactions were obtained. Satisfactory separation capability of various analytes such as alkylbenzenes, polycyclic aromatic hydrocarbons, benzoic acid and its homologs, and (2)-receptor excitants has been achieved. Applied to the real sample, the good resolution of three alkaloids in Corydalis yanhusuo were achieved by pCEC with the quinine-modified monolith. The results light a potential access to facilely fabricating quaternary ammonium-functionalized polymer monolith with multiple interactions for efficient electrochromatography profiling of various compounds.