Rose bengal (RB)-loaded upconverting nanocomposites are synthesized as a near-infrared (NIR)-responsive inhibitor of Aβ aggregation. Rattle-structured, organosilica shell (ROS) is deposited on NaYF4:Yb,Er nanocrystals (UCNPs) for high loading efficiency and disaggregation of RB. RB/UCNP@ROS successfully inhibits Aβ self-assembly under NIR irradiation by generating 1O2. Furthermore, photoexcited RB/UCNP@ROS is effective in suppressing Aβ-induced cytotoxicity.