Nuclear factor-κB (NF-κB) plays an important role in the inflammatory response after intracerebral hemorrhage (ICH). We therefore proposed that NF-κB activation in perihematomal brain tissue might correlate with clinical outcome in patients with ICH. To confirm this, we studied clinical data of 45 patients with ICH and NF-κB activation in perihematomal brain tissue and analyzed predictors of clinical outcome as well as the predictive value of NF-κB activation. Forty-five patients with spontaneous basal ganglia hemorrhage were prospectively investigated. The clinical data were collected, which include demographics, alcohol and tobacco abuse, stroke risk factors, neuroimaging variables at presentation, Glasgow Coma Scale (GCS) at admission, number of days in hospital, mechanical ventilation, pneumonia, and outcome. Clinical outcome was assessed by the modified Rankin Scale at 6 months after ICH. Perihematomal brain tissue was collected, and NF-κB activation was detected using immunohistochemistry. Univariate analysis and multivariate logistic regression analysis were performed to determine predictors of the poor outcome. Immunohistochemical detection showed that NF-κB p65 was expressed in the nuclei of neurons and glial cells in all patients. The number of nuclear NF-κB p65-positive cells was 54 ± 21. Six months after ICH, 18 (40%) patients achieved a favorable functional outcome (mRS ≤ 3) while 27 (60%) had a poor functional outcome (mRS 4 to 6). In univariate analysis, predictors of poor functional outcome were lower GCS score on admission (P = 0.004), larger hematoma volume (P = 0.004), intraventricular extension (P = 0.047), midline shift (P = 0.005), NF-κB activation (P < 0.0001), mechanical ventilation (P = 0.018), and co-morbidity with pneumonia (P = 0.002). In multivariate logistic regression analysis, NF-κB activation was the only independent predictor of poor outcome at 6 months after ICH. NF-κB activation is closely related to clinical outcome 6 months after ICH in humans. Therefore, it could be useful to predict prognosis of ICH accurately and should be further evaluated as a target for therapeutic strategies of ICH in the future.