<i>In vivo</i>, xenograft models further validated that BUB1 silencing significantly reduces tumor volume, accompanied by modulation of ferroptosis-related genes in tumor tissues.<h4>Discussion</h4>Collectively, our findings identify BUB1 as a novel prognostic biomarker and therapeutic target for LUAD, revealing a new regulatory mechanism by which BUB1 promotes LUAD progression through the activation of the STAT3/GPX4 axis to suppress ferroptosis. Here, GPX4 is linked to neoplasm.