Some studies have shown that the co-morbidity of insomnia and anxiety and depression is very prominent, among which 70% of anxiety patients are accompanied by sleep disorders, which is commonly referred to as insomnia of liver depression syndrome in traditional Chinese medicine. The etiology and pathogenesis of traditional Chinese medicine is liver-qi discomfort, and soothing liver and relieving depression should be taken as the basic treatment method and treatment principle. By sorting out the relevant literature on PI3K/Akt signaling pathway, the relationship between PI3K/Akt signaling pathway and depression and insomnia was sorted out, and the possible mechanism of Liver-soothing and Depression-Relieving therapy for insomnia of liver-depression syndrome was found.