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Objective: To study the association between serum neuron-specific enolase (NSE) and the extent of brain damage and the outcome after acute traumatic brain injury (TBI). Methods: The release patts of serum NSE in 78 patients after acute TBI were analyzed by using the enzyme linked immunosobent assay. The levels of NSE were compared with Glasgow coma scale, the category of brain injury and the outcome after 6 months of injury. Results: There were different NSE values in patients with minor (12.96 μg/L±2.39 μg/L), moderate (23.44 μg/L±5.33 μg/L) and severe brain injury (42.68 μg/L±4.57 μg/L). After severe TBI, the concentration of NSE in patients with epidural hematomas was 13.38 μg/L±4.01 μg/L, 24.03 μg/L±2.85 μg/L in brain contusion without surgical intervention group, 55.20 μg/L±6.35 μg/L in brain contusion with surgical intervention group, and 83.85 μg/L±15.82 μg/L in diffuse brain swelling group. There were close correlations between NSE values and Glasgow coma scale (r=-0.608, P<0.01) and the extent of brain injury (r=0.75, P<0.01). Patients with poor outcome had significantly higher initial and peak NSE values than those with good outcome (66.40 μg/L±9.46 μg/L, 94.24 μg/L±13.75 μg/L vs 32.16 μg/L±4.21 μg/L, 34.08 μg/L±4.40 μg/L, P<0.01, respectively). Initial NSE values were negatively related to the outcome (r=-0.501, P<0.01). Most patients with poor outcomes had persisting or secondary elevated NSE values. Conclusions: Serum NSE is one of the valuable neurobiochemical markers for assessment of the severity of brain injury and outcome prediction.