Abstract： AIM To compare the effect of different nutritional support programs on serum protein, inflammatory cytokines, and Glasgow Coma Scale (GCS) score in patients with severe craniocerebral injury (SCCI). METHODS The clinical data of 150 patients with SCCItreated from April 2012 to April 2017 were retrospectively analyzed. Among them, 70 patients were given general enteral nutrition support in the early stage (control group), and 80 patients were given early enteral nutrition support program containing probiotics (observation group). The two groups of patients were compared in serum protein levels, inflammatory cytokines, GCSscore, and other indicators. RESULTS At weeks 1 and 2 after treatment, serum protein levels (39.22±2.58 vs 35.03±1.91, 41.31±2.61 vs 36.92±1.93, P ＜ 0.05) and hemoglobin levels (103.68±11.56 vs94.19±10.81,107.32±11.41 vs 95.12±10.87, P ＜ 0.05) were significantly higher and the levels of IL-6, TNF-a, D-lactate, and PCT (week 1: 87.33±18.61 vs 113.76±20.35, 6.28±1.06 vs 8.22±1.58,1.25±0.21 vs 2.39±0.46,4.15 ± 0.86 vs 7.12±1.01; week 2: 85.35 ± 17.32 vs 110.91±18.93, 5.92±1.01 vs 8.31±1.61,1.09±0.19 vs 2.28±0.37,4.105±0.71 vs 7.08±1.22; P ＜ 0.05) were significantly lower in the observation group than in the control group. GCSscores at weeks 1 and 2 were significantly higher in the observation group than in the control group (12.08±1.52 vs 10.28±1.37,13.26±1.72 vs 11.31±1.41, P ＜ 0.05). The hospitalization time, hospitalization cost, enteral nutrition time, and in-hospital mortality were significantly lower in the observation group than in the control group (21.28±7.16 vs 27.43±8.23, 8.38±1.96 vs 11.65±2.67,17.66±5.71 vs 23.19±7.33,16.25％ vs 28.57％, P ＜ 0.05). The GOSscore at 6 mo after discharge was significantly higher in the observation group than in the control group (4.32±1.25 vs 3.11±0.91, P ＜ 0.05). CONCLUSION The early use of probiotics-containing enteral nutrition regimens in patients with SCCIcan significantly improve nutritional status, reduce inflammatory response, and improve GCSscore.