Objective: GdF3:Tb nanosized phosphors were synthesized by the sol–gel and hydrothermal methods. Directed crystallite growth toward the (020) and (210) crystallographic planes was revealed. Methods: The chemical trap method was used to explore the efficiency of reactive oxygen production of the GdF3:Tb–Rose Bengal photosensitizer system. Results and Discussion: It was shown that the phosphors synthesized by the hydrothermal method have a smaller particle size and a higher luminescence intensity compared to those synthesized by the sol–gel method. Due to their luminescent characteristics and particle size, the GdF3:Tb nanosized phosphors synthesized by the hydrothermal method are suitable for use, in combination with the Rose Bengal photosensitizer, in drug formulations for X-ray photodynamic therapy of oncological diseases. Conclusions: The addition of the GdF3:Tb nanosized phosphors, synthesized by the hydrothermal method, significantly (by 17%) increases the production of reactive oxygen.