This review summarizes the present advance of effects of stress on hippocampal structure and function and the role of hippocampus in feedback regulation of thalamic-pituitary-adrenocortical (HPA) axis during stress. It shows that stress can affect hippocampal structure and function, on the other hand, the hippocampus can also suppress the stress reaction through the feedback regulation of HPA axis, but chronic stress can attenuate this regulation, then significantly impair its structure and function.