Acute rejection that causes liver transplant dysfunction is the most common cause of mortality following liver transplantation. The potential role of Yin Yang 1 (YY1), a widely expressed zinc finger DNA-binding transcription factor, in acute rejection of liver allografts remains unknown. Here, we evaluated the effects and mechanisms of YY1 in an acute rejection using major histocompatibility complex (MHC) class II-mismatched rat liver transplantation model. On days 5 and 10 after liver transplantation, allografts showed elevated expression of YY1 in infiltrating inflammatory cells around the central vein of recipient livers accompanied by elevated levels of serum transaminase and proinflammatory cytokines. In vitro analysis showed that YY1-overexpressing DCs had higher expression of CD80, CD86, and MHC class II compared with the control group. Additionally, YY1-overexpressing DCs triggered naïve CD4+ T cells to produce high levels of intracellular cytokines IL-17 and TNF-γ. These results suggest that YY1 activates DCs and participates in the pathogenesis of acute rejection by polarizing naïve T cells to the inflammatory phenotype, making YY1 a candidate therapeutic target to avoid acute rejection after liver transplantation.