Abstract: Tissue-resident memory T cells (TRMs) are a special type of memory T cells that play an important role in the immune response. They are characterized by the expression of homing receptors, which imparts them resident properties to ensure that they can reside in peripheral tissues and organs, and thus, respond rapidly to invading pathogens. There is increasing research attention on the relationship between TRMs (especially CD8⁺TRMs) and their anti-tumor applications. On the one hand, CD8⁺TRMs directly kill tumor cells by secreting certain cytokines, such as granase B, perforin, and INF-γ. On the other hand, some anti-tumor treatments (such as radiotherapy, chemotherapy, and immunotherapy) enrich CD8⁺TRMs in tumor tissues, which can further improve their therapeutic effect. Here, we review research progress on the classification of CD8⁺TRMs, their regulatory mechanism in tumors, and their applications in cancer therapy.