T-cell activation is an energy expenditure process and should be properly controlled in accordance with the availability ofnutrients such as amino acids to eliminate wasteful energy consumption. However, the details of response to amino acidsinsufficiency in activated T cells remain largely unknown. Here we show that homeobox B9 (HOXB9), a member of thehomeobox gene family that is known as a morphogenesis regulator, acts as a suppressor of activated human T cells to addressamino acid starvation. The expression of HOXB9 was triggered by amino acid deprivation as well as functional inhibition ofL-type amino acid transporter 1 (also known as SLC7A5) via activating transcription factor 4 in activated T cells. HOXB9interfered the activities of NF-κB, nuclear factor of activated T-cells (NFAT) and AP-1 but not retinoic acid receptor-relatedorphan receptor, resulting in attenuation of the production of selective cytokines in activated T cells. Thus, the morphogeneticgene plays an unexpected role in the regulation of cellular metabolism with changes in the nutrition status in human T cells.