An analytical model is developed for predicting the controlled release of platelet-derived growth factor-BB (PDGF-BB) from an aptamer-functionalized hydrogel. The release kinetics are determined by the equilibrium constant of aptamer-protein interactions, which significantly increases the characteristic release time scale. The reduction of the cumulative protein release can also be modulated by tuning the binding affinity of the aptamer. The analysis describes the underlying transport and reaction mechanisms for the controlled protein release well. Particularly, the non-Fickian release kinetics are represented by a self-similar release profile. The model is validated by experiments and direct numerical calculation. It can be applied to release kinetics involving multiple aptamers and proteins.