Objective To explore the correlation of liver depression grading with estrogen receptor alpha and beta(ERα,ERβ)and G protein-couple receptor 30(GPR30)of the perimenopausal women suffering from non-organic insomnia. Methods A total of 127 perimenopausal women suffering from non-organic insomnia were enrolled into the study. The data collected by four diagnostic methods and the scores of Pittsburgh Sleep Quality Index(PSQI)were used for the scoring and grading of liver depression according to Syndrome Element Differentiation. The mRNA and protein expression levels of ERα,ERβand GPR30 in the mononuclear cells of peripheral blood from the patients were detected with real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB)method respectively. Results (1)The differences of mRNA levels of ERα,ERβ and GPR30 were insignificant among the patients with different degrees of liver depression (P > 0.05). ERα mRNA/ERβ mRNA ratio was decreased with the increase of liver depression grading,the differences being significant (F = 6.710, P < 0.001). (2) The differences of protein levels of ERα, ERβ and GPR30 were insignificant among the patients with different degrees of liver depression (P > 0.05);ERα/ERβ protein gray value ratio was decreased with the increase of liver depression grading, and the differences were significant (P < 0.05) . Conclusion The decline of ERα/ERβ is probably contributed to the pathological basis of liver depression in perimenopausal non-organic insomnia women.