Objective To explore the mechanism of granulocyte-colony stimulating factor (G-CSF) on neuronal protective function in acute spinal cord model mice. Methods Hemi-section injury was produced by cutting one-half of the right lateral portions of the spinal cord. After the surgery the mouse accepted an intraperitoneal injection of recombinant human granulocyte colony-stimulating factor(rhGCSF), once a day for 3 days. Behavior of the mouse was analyzed with Basso-Beattie-Bresnahan(BBB) locomotor rating scale. The spinal cord of the mouse was then dissected and examined with histological immunofluorescence and Western blotting analysis. We established neuron mechanical injury model EM>in vitro/EM>. Morphological changes were observed and TUNEL staining was used to investigate the apoptosis. Results In the G-CSF group, improvement in hindlimb motor function was significantly greater than that in the injury group. G-CSF receptor was expressed specifically on the neurons. After treatment with G-CSF in acute spinal cord injury, nucleophosmin 1(NPMI) expression was significantly increased and apoptotic cells decreased. After treatment with NSC348884, a specific nucleophosmin inhibitor, in neuron mechanical injury model EM>in vitro/EM>, apoptotic neurons increased and the function of G-CSF on neuronal protection was decreased.Conclusion G-CSF improves motor function in acute spinal cord injury. Moreover, this protective effect may be achieved through the anti-apoptotic role of NPM 1.