Regulatory T (Treg) cells are a subset of CD4 T lymphocytes characterized by their expression of the transcription factor Foxp3, which dictates their development and function. Treg cells play a vital role in maintaining the balance of the immune response in the body. Tumor cells attract Treg cells infiltration, promoting immune surveillance escape and developing a pro-tumorigenic tumor microenvironment (TME). Reducing Treg cells can effectively amplify the antitumor immune response and tumor eradication in mouse models. The accumulated evidence suggests that the loss of Foxp3 expression causes Treg instability and reprograms to pro-inflammatory cytokine producing effector-like cells. We have uncovered continuing TCR activation and pro-inflammatory cytokines lead to the generation of Foxp3 instability and undergo reprogramming into other effector T subsets called exTreg cells. Loss of Foxp3 expressions in Treg cells results in function loss and expression of inflammatory cytokine. Exploration of the process of transforming Treg cells into effector-like exTreg cells is essential in understanding the pathogenesis of autoimmune disorders and allergic diseases. In addition, it may provide new strategies for fighting tumors and immune disorders.