Social-cognitive processing has been posited to underlie general functions such as episodic memory. Episodic memory impairment is a recognized hallmark of amnestic mild cognitive impairment (aMCI) who is at a high risk for dementia. Three canonical networks, self-referential processing, executive control processing and salience processing, have distinct roles in episodic memory retrieval processing. It remains unclear whether and how these sub-networks of the episodic memory retrieval system would be affected in aMCI. This task-state fMRI study constructed systems-level episodic memory retrieval sub-networks in 28 aMCI and 23 controls using two computational approaches: a multiple region-of-interest based approach and a voxel-level functional connectivity-based approach, respectively. These approaches produced the remarkably similar findings that the self-referential processing network made critical contributions to episodic memory retrieval in aMCI. More conspicuous alterations in self-referential processing of the episodic memory retrieval network were identified in aMCI. In order to complete a given episodic memory retrieval task, increases in cooperation between the self-referential processing network and other sub-networks were mobilized in aMCI. Self-referential processing mediate the cooperation of the episodic memory retrieval sub-networks as it may help to achieve neural plasticity and may contribute to the prevention and treatment of dementia.