Abstract: Objective Based on the "gene-brain-cognition" model, this study explores the association between the polymorphism of rs4860671 in EPHA5 and attention-deficit/hyperactivity disorder (ADHD), and analyzes its impact on executive function and resting-state brain function. Methods Genotype data and resting-state functional Magnetic Resonance Imaging (rs-fMRI) data were collected from children with ADHD and healthy child controls. The Behavior Rating Inventory of Executive Function (BRIEF) was used to assess ecological executive function, while the core symptoms of ADHD were evaluated using the ADHD rating scale. Genetic association analysis, covariance analysis, and mediation analysis were employed to systematically investigate the association of this polymorphism with ADHD clinical symptoms, executive function, and brain activity. Results Allelic and genotypic analyzes showed that the G allele of rs4860671 might be a risk allele for ADHD. The association with cognitive function revealed that GG genotype carriers exhibited poorer emotional regulation, with emotional regulation acting as a full mediator between genotype and core symptoms. Brain imaging analysis showed that GG genotype carriers had reduced spontaneous brain activity in the right calcarine sulcus and left cuneus compared to A allele carriers. Conclusion The polymorphism of rs4860671 in EPHA5 may be involved in the pathogenesis of ADHD by affecting emotional control ability and the functional activity of the visual network, providing new scientific evidence for a deeper understanding of the neurobiological mechanism of ADHD.