Abstract: 　Objective　To explore the clinical features and diagnosis of neonatal chronic granulomatous disease (CGD). Method　The clinical data of CGD in a newborn was retrospectively analyzed. Results　The onset of the disease was in the neonatal period. In addition to the repeated fever, clinical symptoms and positive signs were not obvious. However, there was a history of small pustular rash after vaccination. Respiratory burst function test of neutrophils showed that the stimulation index (SI) was significantly decreased, the aspergillus antigen was positive, and the tuberculosis antibody, PPD test and T-SPOT were all negative. Multiple nodules were visible in CT images of the lung. Anti-infective and symptomatic treatments were not effective, and macrophage activation appeared in the later stage, and the patient died soon after discharge. CYBB gene analysis revealed a hemizygous mutation, c.845_855del (deletion), resulting in amino acid changes of p.E283Afs*61 (frameshift mutation). The mutation is a spontaneous mutation, which does not belong to polymorphisms and happens with very low frequency in the population. Conclusion　CGD should be highly suspected in patients with neonatal onset, reaction or skin infection after vaccination, recurrent fever, decreased SI detected by neutrophil respiratory burst function, and multiple nodules characterized by lung CT imaging. CYBB gene mutation is the common cause of CGD.