INTRODUCTION: Hirschsprung Disease (HSCR) is a common congenital intestinal disease in pediatrics. Early diagnosis and treatment after birth alleviate the occurrence of complications. Consequently, we aim to identifiy a biomarker with ease of use, non-invasiveness, and highly accurate for diagnosis. METHODS: Plasma samples were collected from HSCR group, other intestinal disease controls (DC) and healthy controls (HC) RESULTS: Microarray analysis revealed that the level of plasma N-methyl-D-Aspartate receptor (NMDAR) autoantibody in HSCR group was significantly higher than those in the HC group ( CONCLUSIONS: Plasma NMDAR autoantibody might be served as an efficient, non-invasive biomarker for diagnosing HSCR.