Fragile X syndrome (FXS) is a genetic condition associated with risk for deficits in executive function, especially response inhibition. Under a clinical setting, this study employs a mobile neuroimaging technique, functional near-infrared spectroscopy (fNIRS), to examine differences in inhibition-elicited neural activation between girls with FXS and a control group matched for age, cognitive function, and clinical symptoms. fNIRS data were collected from 42 girls with FXS and 31 controls during a go/nogo task, with valid data available from 35 and 30 respectively. Relative to the control group, girls with FXS showed higher brain activation (NoGo>Go) in the right dorsolateral prefrontal cortex (DLPFC), angular gyrus, precentral gyrus, and left frontal pole, and lower activation in the right ventrolateral prefrontal cortex, frontal pole, precentral cortex, middle temporal cortex, parietal lobe, and left superior temporal cortex. A significant positive correlation was found between DLPFC activation and response inhibition deficits in girls with FXS. Girls with FXS show abnormal neural activation in response to inhibitory stimulus. Aberrant neural activation in DLPFC in girls with FXS is associated with executive function deficits. fNIRS is established to allow participants to engage in a task in relatively more "real world"conditions compared to the scanner environment. © 2025 The Author(s). Published by Oxford University Press. All rights reserved.