Sox11, one of the SoxC family members, is an important transcription factor during neural development and neurogenesis. However, there is no report about its function in neural apoptosis. This research aims to examine the function of Sox11 in surgical brain injury (SBI). We used 90 Sprague-Dawley rats to develop the SBI models and the siRNA of Sox11 to study the roles of Sox11. Western blot, real-time PCR, immunofluorescence, neuron apoptosis and necrosis, brain edema, and neurological score were determined. The gene and protein amount of Sox11, compared with the Sham group, were increased after SBI, which reached a peak at 12 hr. In addition, following the application of siRNAs, the amount of Sox11 protein was significantly less than that in the SBI group. On the other hand, neuronal apoptosis, necrosis, and brain edema were significantly increased, while neurological scores were decreased. These findings demonstrate the role of Sox11 following nerve injury induced by SBI. Inhibition of Sox11 with siRNA may lead to neuronal injury and cell death, aggravating secondary brain injury after SBI.