Massive cerebral infarction (MCI) is a life-threatening disease and may lead to cerebral herniation. Neutrophil degranulation contributes to ischemic injury in the early stage. To investigate whether neutrophil degranulating factors can predict cerebral herniation and the long-term prognosis of patients with MCI and to investigate the relationship between neutrophil degranulation and blood brain barrier (BBB) damage. In this case-control study of 14 MCI patients, we divided the patients into a cerebral hernia group and no cerebral hernia group according to whether they developed cerebral herniation within 5 days. The prognosis of MCI patients was assessed using the Modified Rankin Scale (mRS) score at 6 months, which was the primary end point. The composition of white blood cells (WBC) and degranulating factors for neutrophils in the plasma of MCI patients was determined on days 2 and 4. Baseline characteristics were comparable in both groups. The neurological functional scores and long-term prognosis showed no difference between patients with or without cerebral herniation, while the mortality rate of the cerebral hernia group in the short term was higher (P < 0.05). The WBC count, neutrophil to lymphocyte ratio (NLR) and plasma myeloperoxidase (MPO) levels of patients with cerebral hernia were significantly higher than those of patients without cerebral hernia (all P < 0.05). MPO is a better predictor of cerebral herniation, and the NLR showed superior predictive value in the prognosis of MCI patients. neutrophil degranulation may play an important role in malignant cerebral hernia during MCI. These data suggest that, MPO and the NLR might be predictive factors for cerebral herniation and the prognosis of MCI patients.