Functionalization of mesoporous silica spheres with well-dispersed and ultra-small nanodots to exert their synergistic effects for biomedical applications has been considered to be an urgent challenge.Herein,homogeneously incorporation of ultra-small and monodispersed MoS2 nanodots in the mesoporous silica nanospheres (MSN) was achieved by a facile one-step solvothermal reaction.The as-synthesized UsM-SND@MSN possessed uniform size (～115 nm) and favorable biocompatibility inherited from MSN.The dispersed UsMSND within MSN could act as anchoring sites for aromatic anti-cancer drug DOX loading,and consequently achieved pH-responsive release based on the special π-π/electrostatic interactions with the DOX molecules.More importantly,the well-dispersed UsMSND in MSN could function as the non-toxic contrast agent for the sensitive in vivo CT imaging in various tumors including breast cancer and glioma with different sections.This work promises a good strategy for dispersed incorporation of UsMSND into MSN as an excellent pH-responsive platform for simultaneous cancer imaging and therapy.