Abstract: OBJECTIVE To improve the drug loading capacity of mesoporous silicon nanoparticles(MSNs) and make it photoresponsive. METHODS This study used the template method to prepare aminated mesoporous silica nanoparticles (MSN-NH₂), and induced the efficient loading of chemotherapeutic agent Doxorubicin(Dox) and the photothermal therapeutic agents(Cypate) and Ce6 within MSNs through the calcium ion-driven drug loading strategy(MSN-Ca), resulting in light-responsive MSNs with single or multiple drugs, and their physical and chemical properties and drug release characteristics had been studied. RESULTS Calcium ions could be effectively loaded into MSNs, and they induced the efficient loading of Dox, Cypate and Ce6 in the pores of the MSNs. The drug loading capacities were (28.5±1.4)%, (36.8±1.5)% and (36.6±1.7)%, respectively. MSN-Ca was capable of co-loading two or three drugs among Dox, Cypate and Ce6. The MSNs loaded with Cypate exhibit a photothermal effect. Dox-loaded MSNs had the characteristic of releasing Dox in response to acidic pH. The Doxorubicin release of light-responsive MSN-Ca-Dox/Cypate was enhanced significantly upon laser irradiation at 785 nm. CONCLUSION This calcium ion-driven drug loading strategy plays an important role in the construction of multifunctional MSNs and expedites the development of anti-tumor synergistic therapy.