The antiapoptotic protein BCL2A1 is highly, but very heterogeneously expressed in Diffuse Large B-cell Lymphoma (DLBCL). Particularly in the context of resistance to current therapies, BCL2A1 appears to play an important role in protecting cancer cells from the induction of cell death. Reducing BCL2A1 levels may have therapeutic potential, however, no specific inhibitor is currently available. In this study, we hypothesized that the signaling network regulated by epigenetic readers may regulate the transcription of BCL2A1 and hence that inhibition of Bromodomain and Extra-Terminal (BET) proteins may reduce BCL2A1 expression thus leading to cell death in DLBCL cell lines. We found that the mechanisms of action of acetyl-lysine competitive BET inhibitors are different from those of proteolysis targeting chimeras (PROTACs) that induce the degradation of BET proteins. Both classes of BETi reduced the expression of BCL2A1 which coincided with a marked downregulation of c-MYC. Mechanistically, BET inhibition attenuated the constitutively active canonical nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB) signaling pathway and inhibited p65 activation. Furthermore, signal transducer of activated transcription (STAT) signaling was reduced by inhibiting BET proteins, targeting another pathway that is often constitutively active in DLBCL. Both pathways were also inhibited by the IκB kinase inhibitor TPCA-1, resulting in decreased BCL2A1 and c-MYC expression. Taken together, our study highlights a novel complex regulatory network that links BET proteins to both NFκB and STAT survival signaling pathways controlling both BCL2A1 and c-MYC expression in DLBCL.