Objective: To investigate the effects of oxycodone hydrochloride anesthesia maintenance and pre analgesia on brain tissue protection and early cognitive function in emergency surgery of severe brain injury. Methods: One hundred and twelve patients with severe craniocerebral injury who received emergency craniotomy from October 2018 to December 2019 in the First Affiliated Hospital of Zhengzhou University were included and randomly divided into conventional group (n=56) and oxycodone group (n=56). The conventional group was maintained with propofol and remifentanil, and sufentanil was injected intravenously 15~20 min before the operation, while the oxycodone group was maintained with propofol and oxycodone hydrochloride, and oxycodone hydrochloride was injected intravenously 15~20 min before operation. The monitoring levels of hemodynamics, serum neuron specific enolase (NSE), malondialdehyde (MDA) and high sensitivity C-reactive protein (hs-CRP) were compared between the two groups. Mini Mental State Scale (MMSE) was used to evaluate the early cognitive function of the two groups within 3 months after operation. Results: There was no significant difference in mean arterial pressure (MAP) and heart rate (HR) levels during intubation, intraoperative incision and postoperative in the oxycodone group (P>0.05). MAP and HR at incision in the conventional group were higher than those at intubation time (P<0.05). MAP and HR of the oxycodone group were significantly lower than those of the conventional group at incision and end of operation (P<0.05); the levels of NSE and hs-CRP in the oxycodone group were significantly lower than those in the conventional group after intraoperative dural incision (T1) and 6 hours after operation (T2), and MDA at T2 was significantly lower than that in the conventional group (P<0.05). There was no significant difference in the awake rate between the two groups 3 months after operation (P>0.05). The MMSE score of conscious patients in the oxycodone group was significantly higher than that in the conventional group (P<0.05). Conclusion: oxycodone anesthesia maintenance and pre analgesia in emergency operation of severe craniocerebral injury can not only stabilize hemodynamics, but also reduce oxidative stress and inflammatory reaction in brain tissue, and promote early postoperative cognitive function recovery.