In severe traumatic brain injury (sTBI), acute oxidative stress and inflammatory cascades rapidly spread to cause irreversible brain damage and low survival rate within minutes. Therefore, developing a feasible solution for the quick-treatment of life-threatening emergency is urgently demanded to earn time for hospital treatment. Herein, Janus catalysis-driven nanomotors (JCNs) are carefully constructed via plasma-induced alloying technology and sputtering-caused half-coating strategy. The theoretical calculation and experiment results indicate that the heteroatom-doping alloyed engine endows JCNs with much higher catalytic activity for removing reactive oxygen species and reactive nitrogen species than common Pt-based engines. When JCNs are dropped to the surface of the ruptured skull, they can effectively catalyze endogenous hydrogen peroxide, which induces movement as fuels to promote JCNs to deep brain lesions for further nanocatalyst-mediated cascade-blocking therapy. The results demonstrate that the JCNs successfully block the inflammatory cascades, thereby reversing multiple behavioral defects and dramatically declining the mortality of sTBI mice. This work provides a revolutionary nanomotor-based strategy to sense brain injury and scavenge oxidative stress. Meanwhile, the JCNs provide a feasible strategy to adapt various first-aid scenarios due to their self-propelled movement combined with highly multienzyme-like catalytic activity, exhibiting tremendous therapeutic potential to help people for emergency pretreatment.