Studies have found that depression is closely related to the hyperactivity of the hypothalamo–pituitary–adrenal (HPA) axis, which is manifested in increases in HPA axis-related hormones CRH, ACTH and CORT contents. Traditional Chinese medical acupuncture can down-regulate HPA axis levels to produce a marked antidepressant effect. However, at present there is no HPA axis mechanism analysis of the antidepressant effect of acupuncture. From two aspects: the relationship between depression and HPA axis, and clinical and animal mechanism studies of the antidepressant effect of acupuncture by regulating the HPA axis, an analysis has been made to provide a more powerful scientific basis and the idea of further in-depth study for clinical acupuncture treatment of depression.