Upconversion nanoparticles (UCNPs) represent a new class of nanomaterials that have great potential for use in experimental and clinical oncology. The main feature of UCNPs is ability to convert the infrared radiation (IR), penetrating relatively deep into the tissues of organisms (1-1.5 cm), into visible and ultraviolet (UV) light, inducing the formation of reactive oxygen species (ROS), that can be used for photodynamic therapy (PDT) of malignant neoplasms. In this report, we demonstrate the possibility of PDT of human melanoma using UCNPs covered with biocompatible coatings. It is shown that activation of UCNPs, captured by tumor cells, by 975 nm laser irradiation causes photons upconversion into UV radiation that induces the formation of ROS. Injection and activation of UCNPs led to significant inhibition of human melanoma growth (TGI = 80% ± 5%) in nude mice.