Abstract Identifying signals in the tumor microenvironment (TME) that promote CD8+T cell dysfunction can inform the development of novel approaches to improve anti-tumor T cell responses. Here, we identified Nr3c1, the gene encoding the glucocorticoid receptor (GR), as one of the genes preferentially expressed by dysfunctional CD8+TILs. Glucocorticoids (GCs) are steroid hormones and ligands for the GR. Despite their widespread use, surprisingly little is known regarding the molecular circuitry by which glucocorticoids suppress immune responses. We demonstrate that glucocorticoids are synthesized de novo in the TME and activation of glucocorticoid signaling promotes features of dysfunction, including increased expression of checkpoint receptors like Tim3, PD1, Lag3 and TIGIT, and dampened effector function including decreased production of pro-inflammatory cytokines in both murine and human CD8+T cells. Deletion of GR in CD8+T cells in vivo resulted in loss of dysfunctional phenotype in CD8+TILs concomitant with improved tumor growth control. We thus identified glucocorticoid signaling as a component of immune suppression within the TME and uncovered a molecular mechanism by which it suppresses T cell responses. Glucocorticoids are the mainstay for treating the immune-related adverse events (IRAEs) that develop in patients receiving immune checkpoint blockade. Thus, having a better understanding of the mechanisms downstream of GCs could inform the application of glucocorticoids for suppressing immune responses.