In summary, our study reveals the ROS-driven ubiquitination and degradation of NR4A3 under OGD-R condition and identifies that SMARCB1 is an important regulator for the modification of NR4A3 ubiquitination by direct interaction and provides the promising candidate antioxidant TRIOL for treating pulmonary endothelial barrier impairment in ALI. Here, SMARCB1 is linked to acute respiratory distress syndrome.