Jaundice continues to be a serious health concern and is among the leading causes of deaths during the first days of newborn babies’ lives. Serum bilirubin is currently being exploited in the clinic as a key biomarker for the diagnosis and management of neonatal jaundice. The commonly used methods for serum bilirubin determination in clinical settings are direct spectroscopic measurement and the diazo reaction method. These methods have drawbacks such as low sensitivity, matrix interference, poor stability, high-cost, professional training, less specificity and tedious sample preparation. Thus, it is very urgent to develop a rapid and economical route for sensitive and specific detection of free bilirubin directly in human serum.Surface-enhanced Raman scattering (SERS) has emerged as a powerful analytical technique for biosensing applications with high sensitivity, molecular specificity, powerful multiplex detection capability, and excellent photostability. This talk will present our recent study on the development of a paper-based SERS biosensor for label-free detection of bilirubin in serum. This biosensor comprises multifunctional graphene oxide-gold nanostar (GO-GNS) hybrids decorated on the filter paper. This biosensor combines the enrichment for serum bilirubin and plasmonic enhancement for Raman signals of bilirubin for boosting the label-free detection sensitivity directly in blood serum without the need for additional sample preparation. Our results demonstrated the excellent detection performance for detection of bilirubin directly in serum in a label-free manner, and the detection results were compared with the commercial diazo reaction method, which justifies the clinical effectiveness and suitability of the present paper-based SERS biosensor. We believe that the present paper-based SERS biosensor has great potential for clinical translation in accurate diagnosis of jaundice and other related diseases.