Bilirubin neurotoxicity is a serious consequence of hyperbilirubinemia, which is the most common disease of the neonatal period. Clinically, bilirubin neurotoxicity can result in motor deficit, auditory dysfunction, cerebral palsy, seizure and neurodevelopmental diseases, amongst others. Bilirubin neurotoxicity is one of the major worldwide causes of neonatal brain injury, especially in poorer developing countries. However, the mechanisms of bilirubin neurotoxicity are still unclear. After the failure of attempts targeting neurons in many neurodegenerative disorders, neuroinflammation has become a significant target of research. Here, recent advances concerning neuroinflammation in bilirubin neurotoxicity are reported with a focus on the clinical characteristics of bilirubin neurotoxicity, including age-dependency, region-specificity and its yin-yang properties. Effects of neuroinflammation on blood brain interfaces and treatments targeting neuroinflammation in bilirubin neurotoxicity are also reviewed, which may promote the precision of future treatment of bilirubin neurotoxicity.