The multishell-structured NaYF 4 :Yb,Tm,Nd@NaYF 4 :Yb,Nd@ SiO 2 @ZnO nanospheres were synthesized for the first time by combining active-core/active-shell structured upconversion nanoparticles (UCNPs) with ZnO semiconductor. The composite nanospheres can be used as an efficient NIR-induced photocatalyst. Design of core/shell structure for the lanthanidedoped UCNPs (NaYF 4 :Yb,Tm,Nd@NaYF 4 :Yb,Nd) greatly improved their upconversion luminescence (UCL) efficiency which was attributed to the increase of NIR absorption at 808 nm based on Nd 3+ /Yb 3+ cascade-sensitized UC process and the efficient energy migration from active-shell to active-core. The composite photocatalyst used the enhanced NIR-to-UV upconverted light from UCNPs to realize dye photodegradation and photosterilization. On the basis of the results of the scavenger test, we confirm that the hydroxyl radicals (•OH) were considered as the main reactive species produced in the charge transfer and played a key role in the photocatalytic reaction process, while the superoxide radicals (•O 2 − ) and holes (h + ) as secondary active species also participated in the reaction. As measured by MTT assay, the composite photocatalyst exhibited low cytotoxicity for cells. The possible working mechanism can help us to improve the design and photochemical properties of the multishell-structured photocatalyst with NIR light response.