We show that FoxP3hiCD45RA−CD4+ Treg cells [activated Treg (aTreg) cells] are the predominant cell population among tumor-infiltrating FoxP3+ T cells, and that high aTreg cell-infiltrating content is associated with reduced survival in patients with head and neck squamous cell carcinoma (HNSCC). Here, FOXP3 is linked to head and neck squamous cell carcinoma.