<p>Mild cognitive impairment (MCI) is regarded a potential early stage of Alzheimer’s disease (AD) and associated with a significantly increased risk of progression to AD. This study aims to evaluate whole-brain static functional connectivity (SFC) disruptions with the default mode network (DMN) seed points in patients with MCI by resting-state functional magnetic resonance imaging (rs-fMRI), and to explore whether these disruptions could serve as potential markers for MCI progression to AD. Retrospective rs-fMRI data with MCI (<i>n</i> = 36) and corresponding matched healthy controls (HCs) (<i>n</i> = 26) were collected for comparison. Independent component analysis (ICA) was used to extract DMN regions, and SFC was calculated for four seed points within the DMN. Two-sample t-tests were performed to compare group differences in SFC strength between the MCI and HC groups, and Pearson correlation analyses were conducted. Compared to HCs, the MCI group showed both increased and decreased SFC between four subregions and multiple brain regions, decreased SFC was more widely distributed than increased SFC. Abnormal connectivity was more prominent in the first two key nodes compared to the latter two. Affected regions primarily located in the precuneus, frontal gyri, temporal gyri, postcentral gyrus, caudate nucleus, lingual gyrus, and fusiform gyrus. The SFC value between the right angular gyrus and the right insula was significantly negatively correlated with MoCA scores (<i>r</i> = − 0.385, <i>p</i> &lt; 0.05, FDR-corrected). It reveals a decline in the functional integration capacity within the DMN, as well as complex reorganization and abnormal connectivity patterns between the DMN and other brain networks. The altered interactions between DMN subregions and abnormal brain areas are significantly associated with episodic memory disturbance in MCI.</p>