These data reveal that <i>PRELID1</i> mRNA processing is an important regulator of cell type-specific responses to stress used by multiple cancers and is associated with patient outcomes.<b>Implications:</b> This study suggests that the regulation of PRELID1 expression, by APA and other mechanisms, plays a role in mitochondrial ROS signaling and represents a novel prognostic factor and therapeutic target in cancer.<i></i>.