Objective: To investigate the effect of hyperbaric oxygen therapy on neurological function and limb function in patients with severe craniocerebral injury after operation. Methods: Ninety-two patients with severe craniocerebral injury who were treated in Fuxing Hospital Affiliated to Capital Medical University from January 2017 to December 2019 were selected as the research objects. They were randomly divided into observation group (n=46) and control group (n=46). The changes of National Institutes of Health Stroke Scale (NIHSS) score, Fugl-Meyer Assessment (FMA) score and serum neuron-specific enolase (NSE) and S100 calcium-binding protein β (S100β) level were compared between the two groups before and after treatment. Results: After treatment, NIHSS score and serum NSE, S100β level in both groups were significantly decreased, and the decrease in the observation group was more obvious, the differences were of significant (P<0.05). After treatment, the FMA total scores and upper limbs, lower limbs in both groups were significantly increased, and the increase in the observation group was more obvious, and the differences were of significance (P<0.05). Conclusion: The application of hyperbaric oxygen therapy in patients with severe craniocerebral injury can effectively improve the neurological function and limb function of patients, and promote the postoperative rehabilitation of patients.