This study was designed to synthesize, characterize and investigate the drug inclusion property of a series of novel cationic β-cyclodextrin polymers (CPβCDs). Proposed water-soluble polymers were synthesized from β-cyclodextrin (β-CD), epichlorohydrin (EP) and choline chloride (CC) through a one-step polymerization procedure by varying molar ratio of EP and CC to β-CD. Physicochemical properties of the polymers were characterized with colloidal titration, nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography (GPC) and aqueous solubility determination. The formation of naproxen/CPβCDs inclusion complexes was confirmed by NMR and fourier transform infrared spectroscopy (FT-IR). Cationic β-CD polymers showed better hemolytic activities than parent β-CD and neutral β-CD polymer in hemolysis test. The morphological study of erythrocytes revealed a cell membrane invagination induced by the cationic groups. The effects of molecular weight and charge density of the polymers on their inclusion and release performance of naproxen were also investigated through phase-solubility and dissolution studies. It was found that the cationic β-CD polymers with high molecular weight or low charge density exhibited better drug inclusion and dissolution abilities.