Foxp3 expression and Treg development are critical for maintaining dominant tolerance and preventing autoimmune diseases.Human Mst1 deficiency causes a novel primary immunodeficiency syndrome accompanied with autoimmune manifestations.However, the mechanism by which Mst1 controls immune regulation is unknown.Here we show that Mst1 regulates Treg development/function and inhibits autoimmunity by enhancing Foxp3 expression at both transcriptional and post translation levels.