Owing to the over-expressed level in pheochromocytoma cells, dopamine (DA) provides a unique opportunity to design drug delivery systems for pheochromocytoma treatment. Herein, we developed a DA responsive delivery system for the treatment of pheochromocytoma cells based on mesoporous silica nanoparticles (MSNs) capped with DNA-templated silver nanoparticles (AgNPs). In this system, cytimidine-rich DNA grafted on the MSN was employed as the template to in situ drive the synthesis of AgNPs. The as-formed AgNPs were bound to the contour of DNA and blocked the pores to form the AgNPs capped MSNs (MSN@AgNPs). In the presence of DA, the capped AgNPs would break away from the surface of MSNs due to the reactivity of DA with AgNPs through the formation of Ag-catechol bonds, giving rise to the uncapped pores. Doxorubicin (DOX), as a model drug, was used to form DOX-loaded MSN@AgNPs (DOX@MSN@AgNPs) and then to assess the drug release behaviors from the DA-responsive delivery system. The in vitro studies showed that the DOX@MSN@AgNPs have a higher cytotoxicity to rat pheochromocytoma cell lines (PC-12 cells) when compared to human cervical cancer cell lines (HeLa cells). With these excellent features, we believe that this DA-triggered drug delivery system should promote the development of therapy in pheochromocytoma.