Abstract: The advent of nanoscience and nanotechnology offers unprecedented opportunities in nanomedicine, such as increasing therapeutic efficiency and decreasing undesired side effects in cancer treatment. Photodynamic therapy (PDT) is a non-invasive phototherapy-based method that is applied in the treatment of cancer and other diseases and has important clinical value. PDT can be combined with other therapies to realize the synergistic treatment. The emergence of up-conversion nanomaterials provides a fundamental method to solve the problem of photodynamic therapy of deep tumors. Moreover, the versatile preparation and surface modification methods facilitate the fine-tuning of the emission spectrum of up-conversion nanomaterials and the improvement of the photosensitizer's loading capacity. This study reviews the development in design and application of up-conversion nanomaterials for PDT of cancer.