<p>Ferroptosis contributes significantly to neuronal loss and functional decline after spinal cord injury (SCI). Emerging evidence links the vitamin K (VK) cycle to ferroptosis regulation, but its status and role in SCI remain unknown. Therefore, this study aims to elucidate the role and underlying mechanism of the VK cycle in neuronal ferroptosis post-SCI, thereby providing insights for developing novel therapeutic strategies. We quantified VK₂ levels and examined VK cycle enzyme expression in injured spinal cords after SCI to identify mechanisms of VK₂ reduction. The role of VKORC1L1 in neuronal ferroptosis and motor recovery was assessed via overexpression and inhibition both in vivo and in vitro. Finally, VK₂ supplementation was tested for its effects on ferroptosis, tissue damage, electrophysiological outcomes, and motor function after SCI. VK₂ levels were significantly reduced at the injury site following SCI. Expression of VKORC1L1, a pivotal enzyme in the VK cycle, was found to decrease at the injury site after SCI. Enhancing VKORC1L1 expression reduced neuronal ferroptosis, protected spinal cord tissue, and promoted functional recovery. Conversely, inhibiting VKORC1L1 activity heightened neuronal vulnerability and exacerbated ferroptosis. Additionally, supplementation with VK₂ alleviated neuronal ferroptosis, alleviated spinal cord damage, and improved motor function following SCI. The downregulation of VKORC1L1 disrupts the VK cycle, thereby exacerbating neuronal ferroptosis after SCI. Therapeutic strategies targeting VKORC1L1 upregulation or VK₂ supplementation represent promising avenues for SCI treatment.</p> Graphical Abstract <p></p>