Foxp3+ regulatory T cells （Foxp3+Treg） are a special subset of T cells that prevent other immune cells from attacking the body’s own tissues, and are critical for maintaining immune homeostasis. The forkhead family transcription factor Foxp3 is the master regulator of Foxp3+Treg development and differentiation as well as its functional stability. The alteration of functional stability of Treg cells caused by the changes of Foxp3 protein level has been actively involved in controlling major human diseases including infectious diseases， autoimmune diseases， anaphylactic disease， tumor progression， tumor metastasis， and transplantation immunity. Understanding the function of Foxp3 in regulatory T cells differentiation and development and its functional stability will lead to novel therapeutic approaches for relevant immunological diseases.