The transcription factor nuclear factor-erythroid 2-related-2 (Nrf2) controls cellular redox homeostasis and displays immunomodulatory properties. Hypoxic microenvironment in solid tumors generated by their outgrowth activates Nrf2 which induces the expression of anti-oxidant genes and supports continuous growth and proliferation via metabolic reprogramming. It is easy to imagine that hypoxic situation may affect function of immune cells infiltrated into tumor mass. We have thus questioned how hypoxic condition affect T cell immune response against tumor and the role of Nrf2 is involved. First, tumor infiltrating T cells (TILs) were sorted from tumor mass to investigate the alteration of Nrf2 expression. Interestingly, we found that mRNA levels of Nrf2 are significantly increased in TILs compared to control T cells. In order to test whether T cell responses are affected by Nrf2 levels, we stimulated T cells and measured Nrf2 expression. Nrf2 expression and their target genes are significantly downregulated by TCR activation. We further confirmed that IFN-γ production in Nrf2 deficient T cells was dramatically enhanced. Our findings offer novel insights into how immune response and oxidative stress is integrated in tumor cells, and we highlight Nrf2 as candidate of molecular target to control tumor in hypoxic condition.