Objective: To observe the value of amplitude integrated electroencephalogram (aEEG) combined with high sensitivity C-reactive protein (hsCRP) level in early diagnosis of premature infant brain injury (BIPI). Methods: Seventy-five premature infants with brain injury admitted to our hospital from July 2017 to July 2018 were selected as observation group, and 75 normal newborns in the same period were selected as control group. The levels of aEEG and hsCRP were monitored. The differences of EEG background activity, voltage continuity, sleep-wake cycle, seizure and epilepsy situation between the two groups were compared. hsCRP level was also detected. Finally, the sensitivity and specificity of aEEG and hsCRP in the diagnosis of BIPI were discussed from the aspect of combined detection. Results: The abnormal rate of aEEG background activity, voltage continuity, sleep-wake cycle, seizure and epilepsy situation in the observation group was significantly higher than that in the control group (P<0.05). The hsCRP level in the observation group was significantly higher than that in the control group, and the normal hsCRP rate was lower than that in the control group (P<0.05). The combined detection of aEEG and hsCRP could effectively improve the specificity of diagnosis. Conclusion: aEEG and hsCRP have important diagnostic value for early detection of brain injury in children with BIPI. The combined examination of aEEG and hsCRP can significantly improve the clinical diagnostic effect of BIPI.