A novel cancer cell lysosome-targetable multifunctional NO-delivery nanoplatform (Lyso-Ru-NO@FA@C-TiO₂) (1) was developed. It selectively targets folate-receptor overexpressed cancer cells and specifically locates within the lysosome organelle to which NO and reactive oxygen species are simultaneously released upon 808 nm NIR light irradiation. The dual-targeted nanoplatform (1) demonstrated the highest anticancer efficacy compared with nontargeted counterparts under NIR light sensitization.