Abstract: Objective Acute bilirubin encephalopathy (ABE) is an important factor affecting the quality of life of newborns. Early symptoms are not significant, so clinical diagnosis is difficult. This paper discusses the application value of resting-state functional magnetic resonance imaging in neonatal bilirubin encephalopathy. Methods Fifteen children with acute bilirubin encephalopathy and 14 full-term normal infants were selected from the Affiliated Hospital of Hangzhou Normal University from December 2015 to December 2017. Two groups of newborns were examined by resting MR imaging. The images were processed by MATLAB, SPM and DPARSF software. At last, the changes of brain function were compared by low frequency amplitude method, differential brain regions of ALFF values were obtained in two groups. Results Compared with normal full-term infants, acute bilirubin encephalopathy children showed abnormal increase in peak intensity of low-frequency amplitude in temporal lobe, anterior central gyrus and frontal pole (all P<0.05), and significant difference in peak intensity of ALFF in occipital lobe, parietal lobe, left cerebellum and right cerebellum, which were 6.85, 5.02 and 3.34 respectively, compared with normal control group. The peak value of ALFF intensity decreased (all P<0.05), and the difference was statistically significant. Conclusion Compared with normal newborns, bilirubin encephalopathy children have abnormal brain function changes in temporal lobe, anterior central gyrus, frontal pole, occipital lobe, parietal lobe and cerebellum, which may be related to the location of clinical phenotypes in the brain of bilirubin encephalopathy children. Resting-state functional magnetic resonance imaging has important value in early diagnosis of neonatal bilirubin encephalopathy.