Abstract: tRNA (transfer RNA) is the most highly modified RNA in mammalian cells. Their modifications are highly dynamic and easily affected by environmental conditions. Notably, tumor occurrence is often accompanied by abnormal tRNA modifications. Studies have revealed abnormal expression of tRNA-modified enzymes in a variety of tumor tissues, thereby associating them to pathogenesis of the disease. Glioma is the most common primary tumor of the central nervous system having the highest incidence of malignancy and poor prognosis. This study provides a comprehensive review of several tRNA modifications associated with gliomas, describing their functions and mechanisms in the occurrence and development of these tumors. We aimed to investigate the potential of aberrantly modified tRNAs and their derivative fragments as biomarkers in glioma diagnosis and propose novel strategies for glioma therapy using small molecule inhibitors that target epigenetic regulatory factors.