Abstract In this work we adapt rare-earth-ion-doped NaYF₄ nanoparticles coated with a silicon oxide shell (NaYF₄:20%Yb,0.2%Tm@SiO₂) for biological and medical applications (for example, imaging of cancer cells and therapy at the nano level). The wide upconversion emission range under 980 nm excitation allows one to use the nanoparticles for cancer cell (4T1) photodynamic therapy (PDT) without a photosensitizer. The reactive oxygen species (ROS) are generated by Tm/Yb ion upconversion emission (blue and UV light). The in vitro PDT was tested on 4T1 cells incubated with NaYF₄:20%Yb,0.2%Tm@SiO₂ nanoparticles and irradiated with NIR light. After 24 h, cell viability decreased to below 10%, demonstrating very good treatment efficiency. High modification susceptibility of the SiO₂ shell allows for attachment of biological molecules (specific antibodies). In this work we attached the anti-human IgG antibody to silane-PEG-NHS-modified NaYF₄:20%Yb,0.2%Tm@SiO₂ nanoparticles and a specifically marked membrane model by bio-conjugation. Thus, it was possible to perform a selective search (a high-quality optical method with a very low-level organic background) and eventually damage the targeted cancer cells. The study focuses on therapeutic properties of NaYF₄:20%Yb,0.2%Tm@SiO₂ nanoparticles and demonstrates, upon biological functionalization, their potential for targeted therapy.