Polyaniline (PANI) chains with different lengths were grafted onto the surface of hollow mesoporous silica spheres (HMSs) by in situ chemical oxidative polymerization. In the cargo-loading experiments, HMSs-PANI(L) with long PANI chains was unsuitable to load Doxorubicin (DOX) hydrochloride molecules because of channel blockage. In contrast, the oligomer of PANI chains served as the gate, and when grafted onto HMSs (HMSs-PANI(S)), they simply manipulated the “opening” or “closing” of mesopores through the doping mechanism of PANI chains. Utilizing the different states of PANI chains led to the different interaction forces between PANI chains and cargo molecules, and HMSs-PANI(S) can effectively load different cargo molecules. When stimulated by using an acid, the acid-controlled release behaviors of DOX and Rhodamine 6G (R6G) were achieved. When stimulated by using an acid, alkaline controlled release behavior was also observed by loading indomethacin (IND) molecules.