Herein we discuss the role of YY1 as a transcription factor in the regulation of CD8 T cell function and immune evasion, the significance of LAG-3 and YY1 expressions on anti-tumor CD8 T cells and immune evasion, the molecular regulations of the expression of LAG-3 on CD8 T cells, the mechanisms by which YY1 regulates the expression of LAG-3, bioinformatic analyses on the YY1-LAG-3 axis in various cancers, approaches to therapeutically targeting YY1, and future directions and challenges for clinical therapeutic applications. The gene discussed is CD8A; the disease is cancer.