In this review, we will introduce the influencing mechanisms of mitochondrial abnormalities on the anti-tumor effect of CD8+ T cells, which may involve mitochondrial energy metabolism, mROS production, mitochondrial dynamic process, CD8+ T cell apoptosis mediated by mitochondria, mitochondrial membrane potential (MMP), and mitochondrial Ca2+ signaling regulation, as well as the possible efficient ways to treat cancer by targeting mitochondria to improve the anti-tumor function of CD8+ T cells. The gene discussed is CD8A; the disease is cancer.