Organic-inorganic hybrid mesoporous organosilica has gained more attention in biomedicine due to its high surface area, mesoporous channels, functional framework, and high drug loading capacity. In this study, disulfide- bridged hybrid mesoporous organosilica nanoparticles (MONs) as nanocarriers were employed to construct a nanosystem (ICG/DOX-MONs@DNA₂₀) for delivering drugs and photothermal agents, in which DNA molecules as “switches” were modified on the surface of MONs to control drug release. The results showed that the ICG/DOX-MONs@DNA₂₀ nanosystem could increase the temperature to above 43 ℃ for photothermal therapy with near-infrared (NIR) laser irradiation. On the other hand, the ICG/DOX-MONs@DNA₂₀ nanosystem exhibited a very slow release of DOX (12.3% in 6 h) at 37 ℃, but a rapid release of DOX (52.4% in 6 h) occurred at 43 ℃. Cell culture experiments indicated that the nanosystem can be internalized by HeLa cells, and exhibited an enhanced therapeutic efficacy of synergistic chemo- and photothermal therapy. Hence, the ICG/DOX-MONs@DNA₂₀ nanosystem might be promising for synergistic chemo- and photo-thermal tumor therapy.