Abstract： Objective:To explore the effects of hyperbaric oxygen（HBO）combined with gangliosides on serum inflammatory factors，NSE，and Bcl-2 in neonates with hypoxic ischemic encephalopathy（HIE）.Methods:A total of 200 neonates with HIE admitted to the Affiliated Hospital of Jining Medical University from January 2019 to January 2021 were selected and divided into observation group and control group according to the random number table method，with 100 cases in each group. Based on conventional treatments such as oxygen inhalation and intracranial pressure reduction，the control group was treated with ganglioside，and the observation group was treated with HBO combined with ganglioside treatment. After two courses of treatment，the clinical efficacy and the changes of serum inflammatory factors，NSE，and Bcl-2 were compared between the two groups.Results:The total effective rate of the observation group was significantly higher than that of the control group at 1，2，and 3 weeks after treatment and the difference was statistically significant（ P<0.05）. The disappearance time of clinical symptoms of the observation group was shorter than that of the control group，and the difference was statistically significant（ P<0.05）. There was no significant differences in the serum levels of hypersensitivity C-reactive protein（hs-CRP），tumor necrosis factor alpha（TNF-α），interleukin 6（IL-6），NSE，and Bcl-2 between the two groups before treatment（ P>0.05）. At 1，2，and 3 weeks after treatment，the serum levels of hs-CRP，TNF-α，IL-6，NSE，and Bcl-2 of the two groups were significantly lower than those before treatment，and the serum levels of all indexes of the observation group were significantly lower than those of the control group，and the differences were statistically significant（ P<0.05）. The serum levels of NSE and Bcl-2 of the observation group were lower than those of the observation group at 1 and 3 months of follow-up，and the differences were statistically significant（ P<0.05）. The total incidence of sequelae of the observation group was lower than that of the control group，and the difference was statistically significant（ P<0.05）. Conclusion:HBO combined with gangliosides in the treatment of neonates with HIE can improve the curative effect，reduce the serum levels of inflammatory factors，NSE，and Bcl-2，shorten the disappearance time of clinical symptoms，and improve the prognosis of neonates，which has important clinical application value.