Objective To investigate the effect of hyperbaric oxygen on cognitive function and high sensitivity c-reactive protein (hs-CRP) level in patients with severe craniocerebral injury. Methods From Mar. 2016 to Mar. 2017, 120 cases of severe craniocerebral injury patients in our hospital were divided into observation group (n=60) and control group (n=60) according to their treatment methods. Both groups were given routine treatment, besides, the observation group was given additional hyperbaric oxygen. The therapeutic effects, HDS scores, CDR scores and serum hsCRP levels before and after treatment in the two groups were compared. Results The total effective rate in the observation group was (96.67%) which was significantly higher than that in the control group (80%), the difference was statistically significant (P<0.05), after treatment, the HDS score in the observation group was (23.51±4.52) which was significantly higher than that in the control group (16.59±4.22), and the CDR score in the observation group was (0.52±0.41) which was significantly lower than that in the control group (1.15±0.68), the difference was statistically significant (P<0.05), the hs-CRP level in the observation group after treatment was (1.77±1.07) which was significantly lower than that in the control group(5.92±1.90), the difference was statistically significant (P<0.05). Conclusion The adjuvant therapy of hyperbaric oxygen can significantly improve the cognitive function and inflammatory response of patients with severe craniocerebral injury, thus, it is worthy of clinical promotion.