Background <p>Intracerebral hemorrhage (ICH), a subtype of hemorrhagic stroke, is associated with high morbidity and mortality. This study aimed to investigate the role and underlying mechanism of bromodomain and extraterminal domain protein 4 (BRD4) in neural injury following ICH.</p> Methods <p>An in vitro ICH model was established by treating SH-SY5Y cells with hemin. BRD4 and activating transcription factor 3 (ATF3) expression levels were altered using short hairpin RNA and pcDNA3.1 expression vectors. Cell viability and death were assessed using Cell Counting Kit-8 (CCK-8) and TdT-mediated dUTP nick-end labeling (TUNEL) assays. mRNA and protein expression levels were quantified by RT-qPCR and western blotting, respectively. Cytokine secretion was measured using enzyme-linked immunosorbent assay (ELISA) kits. Ferroptosis was evaluated based on levels of reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), and Fe²⁺. Chromatin immunoprecipitation (ChIP) was performed to examine the interaction between BRD4, histone 3 lysine 27 acetylation (H3K27ac), and the ATF3 promoter. </p> Results <p>BRD4 expression was upregulated in hemin-treated SH-SY5Y cells, and its knockdown repressed inflammation and ferroptosis&#xa0;induced by hemin. ATF3 expression was also elevated upon hemin stimulation and was identified as a downstream target of BRD4. Mechanistic studies revealed that BRD4 cooperated with H3K27ac to bind the ATF3 promoter, thereby promoting ATF3 transcription. Functional rescue experiments further demonstrated that ATF3 overexpression counteracted the inhibitory effects of BRD4 knockdown on hemin-induced inflammation and ferroptosis.</p> Conclusions <p>BRD4 silencing alleviated hemin-induced neuronal ferroptosis and inflammation by regulating ATF3 transcription, suggesting that BRD4 inhibition may represent a potential therapeutic strategy for ICH.</p>