<p>Mitochondrial RNA modifications refer to modifications that occur across various RNA species within the mitochondria. While the incidence of such modifications is lower than that in the cytoplasm, substantial evidence highlights their pivotal role in facilitating mitochondrial gene expression and precise protein synthesis. Emerging research suggests that these mitochondrial RNA modifications are also significantly involved in the progression of cancer. In this review, we first delve into the diversity of mitochondrial RNA modifications, their potential sites of occurrence, and the enzymes involved in these processes. We evaluate the existing evidence regarding mitochondrial RNA modifications and their significance in cancer progression and investigate the potential of these modifications as promising targets for both preventative strategies and early diagnostic screening. Finally, we deliberate on the trajectory of mitochondrial RNA modifications in the context of cancer progression and how these RNA modifications might pave the way for novel diagnostic and therapeutic approaches for preventive medicine.</p>