Supramolecular hydrogels were facilitated by alpha-cyclodextrin (α-CD) and three silicone surfactants named S1E8, S1E19 and S2E38, respectively. Influences of the molecular structure and concentration of the silicone surfactants on the formation of hydrogels and their stabilities were investigated. The hydrogels were characterized by phase behavior study and various techniques. The results indicated that the balance between the hydrophilicity and the hydrophobicity of the silicone surfactants is crucial for the formation and high stability of the hydrogels. S2E38, which has two poly-(ethylene oxide) chains, exhibits a stronger ability to form hydrogels than S1E8 and S1E19 do. Moreover, in vitro study using doxorubicin (DOX) as a model anticancer drug shows that α-CD/silicone surfactant hydrogels can be used as injectable carriers for controlled drug release.