OBJECTIVE： To investigate the effects of erythropoietin （EPO） combined with hyperbaric oxygen on neurologic function recovery and cerebral tissue metabolism of hypoxic-ischemic encephalopathy （HIE）. METHODS： A total of 47 HIE neonates in our hospital during Sept. 2012-Apr. 2015 were selected and divided into observation group （25 cases） and control group （22 cases） according to random number table. Both groups received routine symptomatic supportive treatment as reducing intracranial pressure， correcting acidosis， maintaining electrolyte balance and controlling seizures. Control group was given hyperbaric oxygen therapy， compressing 15 min， inhaling 30 min， decompressing 15 min， qd. Observation group was additionally given rhEPO injection （CHO cell） 200 U/kg， subcutaneously at the first time， intravenous injection from the second time， qd. Both groups were treated for consecutive 10 d. NBNA score， neural reflex recovery time， consciousness recovery time， the serum levels of NSE， MBP and S100B protein were observed in 2 groups before and after treatment. The occurrence of ADR was recorded. RESULTS： Before treatment， there was no statistical significance in NBNA score， serum levels of NSE， MBP and S100B protein between 2 groups （P＞0.05）. Five and ten days after treatment， NBNA scores of 2 groups were increased significantly compared to before treatment， and the observation group was significantly higher than the control group at corresponding period， with statistical significance （P＜0.05）. The serum levels of NSE and S100B protein in 2 groups were decreased significantly compared to before treatment， and the observation group was significantly lower than control group at corresponding period， with statistical significance （P＜0.05）. After 5 days of treatment， serum levels of MBP in 2 groups were increased significantly compared to before treatment， with statistical significance （P＜0.05）， but there was no statistical significance between 2 groups （P＞0.05）. After 10 days of treatment， serum levels of MBP in 2 groups were decreased significantly， and the observation group was significantly lower than control group， with statistical significance （P＜0.05）. After treatment， neural reflex recovery time and consciousness recovery time of observation group were significantly shorter than control group， with statistical significance （P＜0.05）. There was no statistical significance in the incidence of ADR between observation group （8.00％）  and control group （9.09％） （P＞0.05）.  CONCLUSIONS： For HIE neonates， EPO combined with hyperbaric oxygen can effectively promote neurologic function recovery and cerebral tissue metabolism with good safety.