Recent studies from the Alzheimer's Disease Neuroimaging Initiative(ADNI) show that 75% of AD are female in the United States. To date, there is rarely attempt to analyze data by sex or gender, which limits the potential for discovering the effects of sex or gender on disease. Little evidence is available regarding the effect of gender and APOEε4 on white matter (WM) connection from the functional perspective for the lack of appropriate technique of detecting BOLD signals in white matter. We took advantage of a new framework known as functional tensor imaging to investigate the effect of sex and APOE4 on WM-cortical functional connectivity throughout the brain. In aMCI female group, we found a significant reduced functional connectivity in left posterior limb of internal capsule, left superior fronto-occipital fasciculus, bilateral temporopolar area, and right somatosensory association cortex in APOE ε4 carriers in contrast to non-carriers. We also found a significant APOE ε4 by sex interaction effect on right somatosensory association cortex, left temporopolar area and left superior temporal gyrus. The clinical MoCA score was significantly negative associated with the right somatosensory association cortex with APOE ε4 by sex interaction in male. These results indicate that increased APOE-related risk in women may be associated with decreased activity in both gray matter and white matter in aMCI compared to men. The finding suggests accounting for sex differences in neuroimaging biomarkers, diagnostics, and treatment strategy. This article is protected by copyright. All rights reserved.