This study aimed to analyze the changes in brain networks functional connectivity of pilots exposed to simulated hypoxia using resting-state functional magnetic resonance imaging (fMRI). A total of 35 healthy male pilots exposed to 14.5% oxygen concentration (corresponding to an altitude of 3000 m) underwent resting-state fMRI scans. The independent component analysis (ICA) approach was used to analyze changes in the resting-state brain networks functional connectivity of pilots after hypoxic exposure, and 9 common components in brain functional networks were identified. In the functional connections that showed significant group differences, linear regression was used to examine the association between functional connectivity and clinical characteristics. The brain networks functional connectivity after hypoxia exposure decreased significantly, including the left frontoparietal network and visual network 1-area, left frontoparietal network and visual network 2-area, right frontoparietal network and visual network 2-area, dorsal attention network and ventral attention network, dorsal attention network and auditory network, and ventral attention network and visual network 1-area. We found no correlation between the altered functional connectivity and arterial oxygen saturation level. Our findings provide insights into the mechanisms underlying hypoxia-induced cognitive impairment in pilots.Abbreviations: AN = attention network, AudN = auditory network, DMN = default mode network, fMRI = functional magnetic resonance imaging, FPN = frontal parietal network, GIFT = group ICA of fMRI toolbox, ICA = independent component analysis, SpO 2 = peripheral oxygen saturation, VN = visual network, WM = working memory.