Abstract： Objective To investigate the efficacy of hyperbaric oxygen ( HBO ) combined with ganglioside on diffuse axonal injury and effects on serum-related indicators and prognosis. Methods Eighty-two patients with diffuse axonal injury admitted into our department were equally divided into 2 groups ( n=41 ) , according to different treatment methods. The control group was given such symptomatic supportive treatment as hormone, hemostasis, reduction of intracranial pressure via dehydration, nerve nutrition, maintenance of electrolyte balance, fluid infusion and routine nursing care. The study group was treated with HBO therapy combined with ganglioside in addition to the treatment received by the control group. The rate of consciousness and mean conscious recovery time, serum-related indicators, cognitive function and prognosis after treatment were compared between the patients of the 2 groups. Results After treatment, the rate of consciousness (80. 5％) and mean conscious recovery time of the study group ( 9. 3 ± 1. 4days ) were all superior to (56. 1％)and (16. 1 ± 3. 3 days) of the control group (χ2 =5. 632, t=6. 349, P<0. 05). After treatment, the levels of neuron-specific enolase (NSE) (11. 1 ± 2. 3 μg/L), S100 calcium binding protein B (S100B) (1. 1 ± 0. 1 ng/L) and myelin basic protein (MBP) (6. 6 ± 1. 2μg/L) were all significantly better than (16. 7&nbsp;±3.1)μg/L,(1.6±0.2)ng/L and(8.5 ±1.0)μg/L of the control group (t1 =4.684, t2 =5.219, t3 =4. 352, P<0. 05). Following treatment, the MMSE scores (28. 3 ± 5. 3) and ADL scores (25. 1 ± 1. 1) of the study group were significantly better than the MMSE scores (25. 2 ± 4. 1) and ADL scores (33. 6 ± 1. 5) of the control group (t1 =4. 429, t2 =5. 642, P<0. 05). Six months after treatment, the prognosis rate of the study group (73. 2％) was significantly higher than that of the control group (41. 5％) (χ2 =8. 424, P<0. 05). Conclusion HBO combined with ganglioside could produce better therapeutic effects in the treatment of diffuse axonal injury. In the meantime, it could avoid deterioration of secondary brain injury to the largest extent and promote recovery of nerve function, and ultimately improve the prognosis of patients. For this reason, it is worth further clinical application.