Natural Killer (NK) cells are the primary effector lymphocyte of the innate immune system. They mount an early and rapid cytotoxic response against pathogens and tumor cells. NK cells recognize tumors and clear them through cytotoxic mechanisms such as the release of cytokines or cytolytic molecules granzyme B and perforin. In this manner, NK cells contribute to the immuno- logical protection against cancer. However, not all cancer cells are efficiently eliminated by the immune system. An important example are breast cancer cells that escape from NK killing and this has been implicated in metastatic pro- gression. To elucidate how cancer cells might escape form NK cell-mediated killing, we performed a genome-wide CRISPR/Cas9 knockout (KO) screen in MCF-7 breast cancer cells. The screen identified the loss of bromodomain-containing protein 9 (BRD9) as a critical factor that promotes tumor evasion from NK cell killing. BRD9 is a member of a non-canonical SWI/SNF chromatin remodeling complex (ncBAF) that regulates gene transcription through altering chromatin accessibil- ity and recruiting transcription factors. Intriguingly, the disruption of a related SWI/SNF chromatin remodeling complex, polybromo BAF (pBAF) has previ- ously been implicated as a sensitizer to CD8 T cell-mediated killing. Our results indicate that the disruption of distinct BAF complexes, ncBAF and pBAF, have opposing effects on immune cell-mediated cancer cell elimination. We confirmed escape from NK cell killing upon BRD9 loss across multiple in- vitro and in-vivo experimental systems. These include isolated human primary NK cells, the immortalized cell line NK-92, in addition to melanoma and colon cancer mouse models. Specifically, we found that the loss of BRD9 in MCF-7 cells had the strongest protective effect against the inflammatory cytokine inter- feron (IFN)-γ that is a key part of the NK mediated anti-tumor response. The loss of BRD9 effectively silenced the transcriptional response to IFN-γ including chemoattractants (CXCL9, CXCL10, CXCL11), cell death regulators (numerous caspases, CTSD, GSDMD) and calcium-dependent pro-inflammatory molecules (S100P, TRPM2). Strikingly, the transcriptional effects were the mirror image of changes observed in cells deficient in the pBAF component PBRM1, which was previously shown to increase sensitivity to T cell-mediated killing. Hence, the BRD9 component of ncBAF and the PBRM1 component of pBAF emerge as crit- ical and opposing regulators of effective cancer cell elimination by cytotoxic immune cells. Next, we examined potential avenues to restore sensitivity for cell death in the BRD9-deficient cells. We speculated that inactivation of the pBAF complex may re-sensitize these cells and reverse the effects of BRD9 loss. We disrupted the pBAF complex genetically by targeting its BRD7 and PBRM1 components in the BRD9-deficient cells and found that these genetic modifications partially restored sensitivity to IFN-γ-mediated cell death. Subsequent genome-wide as- sessment of transcriptional regulation corroborated that targeting pBAF was insufficient to reverse the transcriptional dysregulation caused by the loss of BRD9. We also noticed that the BRD9-deficient cells showed collateral sensitiv- ity to tumor necrosis factor (TNF)-mediated cell death, and this was reflected in the reduced expression of numerous TNF signaling inhibitors including TN- FAIP2, TNFAIP3, and TNFAIP8. Specifically, the treatment of BRD9-deficient cells with TNF-α or TNFSF10 (TRAIL) alone and in combination with IFN-γ en- hanced cell death. Together, these findings highlight the pharmacological block- ade of pBAF and co-treatment with TNF-α and TRAIL as promising strategies to eliminate cancer cells bearing BRD9 mutations.