Various in situ injectable hydrogels have been developed for protein delivery in treating human diseases. However, most hydrogels are highly permeable, which can lead to the rapid release of loaded proteins. The purpose of this study is to apply nucleic acid aptamers to functionalize an in situ injectable hydrogel model to control the release of proteins. The aptamers were studied using secondary structural predictions and binding analyses. The results showed that the structural, predictions were different from the experimental measurements in numerous cases. The affinity of the aptamer was signififantly affected by the mutations of the essential nucleotides, whereas it was not significantly affected by the variations of the nonessential nucleotides. The mutated aptamers were then used to funcnonalize the injectable hydrogel model. The reults showed, that the aptarner-functionalized hydrogel could prolong protein release. Moreover, the release rates could be controlled by adjusting the affinity or the aptamer.