Spinal cord injury (SCI) represents a significant clinical challenge. Following SCI, the implementation of protective measures for neurons is critically important. Current clinical applications of hormone pulse therapy exhibit variable efficacy and considerable side effects, highlighting an urgent need for therapeutic strategies. This study investigates the pathological conditions of ischemia and hypoxia in the SCI region, complemented by early transcriptome sequencing postinjury. Our findings suggest that targeting ferroptosis is pivotal for early neuroprotection following SCI. Aiming at the cascade effect of mitochondrial damage leading to reactive oxygen species (ROS) production, along with extensive ROS-mediated lysosomal damage during ferroptosis signaling, we developed a liposome-based system for regulating iron metabolism─DTLS@CAT. This innovative liposome is designed to specifically target neuronal mitochondria, effectively eliminate mitoROS, and modulate complex interactions among iron metabolism, mitochondria, lysosomes, and ROS to facilitate recovery from SCI.