The surface molecular imprinting technique has been proposed as a prospective strategy for template molecule recognition and separation by devising the recognition sites on the surface of imprinted materials. The purpose of this study was to establish a novel drug delivery system which was developed by surface molecular imprinting method using beta-cyclodextrin (beta-CD)-grafted chitosan (CS) (CS-g-beta-CD) microspheres as matrix and sinomenine hydrochloride (SM) as the template molecule. By adjusting the amount of functional monomer and cross-linking agent, we got the more excellent adsorption of CS-g-beta-CD molecularly imprinted polymers (MIPs-CS-g-beta-CD). When the amount of functional monomer was 6 mmol and cross-linking agent was 20 mmol, the maximum binding capacity of MIPs and non-imprinted polymers (NIPs) was 55.9 mg/g and 37.2 mg/g, respectively. The results indicated that the recognition of SM with MIPs was superior to NIPs. The adsorption isotherms of MIPs-CS-g-beta-CD indicated that the adsorption behavior fitted better to the Langmuir model, which showed that the adsorption process of polymer was monomolecular layer. In in vitro drug release studies, the accumulative release amount of MIPs-CS-g-beta-CD was up to 78% within 24 h. MIPs exhibited an excellent controlled SM release profile without burst release and the mechanism of SM release was shown to conform to non-Fick diffusion. Therefore, MIPs-CS-g-beta-CD were successfully applied to extraction of SM and used as the materials for drug delivery system.