FOXA1 is a pioneer transcription factor that is essential to mitogenic steroid receptor function in hormone-dependent adenocarcinomas, including breast and prostate cancers. FOXA1 is also expressed in other tumor types of epithelial lineage such as NSCLC, but whether and how it is required for tumor growth in these contexts is not known. Herein, we describe a subset of NSCLC that exhibits FOXA1-dependence, present a mechanism for FOXA1-driven NSCLC growth involving the glucocorticoid receptor (GR) and evaluate strategies for therapeutically targeting the FOXA1/GR growth program in this context. NSCLCs typically harbor somatic mutations activating the RAS-MAPK signaling cascade, which is thought to be the key driver of growth in these tumors. Analyzing data from genome-scaled pooled loss-of-function screens, we have identified and validated a subset of MAPK-pathway-mutated NSCLC cell lines with reduced cellular fitness following FOXA1 knockout. Because the growth-promoting functions of FOXA1 in breast and prostate cancers are carried out via cooperation with lineage-defining transcription factors, we performed a RIME screen to nominate candidate factors that may cooperate with FOXA1 in NSCLC to drive oncogenic transcription programs. This screen revealed a chromatin-localized interaction between FOXA1 and GR. We show that depletion of GR expression suppresses the proliferation of a subset of FOXA1-dependent NSCLC models. Using ChIP-sequencing and gene-set enrichment analyses, we demonstrate that FOXA1 and GR co-regulate gene targets involved in growth-factor signaling and cell cycle progression. As pharmacologic inhibition of FOXA1-cooperating factors is a mainstream treatment approach in FOXA1-dependent breast and prostate cancers, we speculated that antagonism of GR in FOXA1-dependent NSCLCs may similarly be an effective therapeutic modality. Using gene-expression and immunoblot analyses of shared FOXA1/GR targets, cell-cycle profiling and proliferation assays, we conclude that reversal of GR transactivation, or neutral antagonism alone is insufficient to block GR-dependent proliferation. Instead, we show that small molecule GR ligands that possess inverse agonistic properties effectively suppress FOXA1/GR target expression, activation of growth factor signaling, entry into S-phase and attendant proliferation. We further show that inverse agonists of GR can effectively slow tumor growth of cell line xenografts in vivo. Finally, we demonstrate that small-molecule downregulation of GR using bi-functional degraders phenocopies the signaling and growth effects of inverse agonists. Taken together, our findings establish a model of FOXA1/GR-dependent tumor growth amongst a subset of NSCLCs and provide rationale for exploring therapeutic targeting of this complex in the clinic.