Abstract: Objective To investigate the expression of endoplasmic reticulum stress-related genes and microRNA-16, microRNA-124 and microRNA-195 in peripheral blood of depressive patients. Methods A total of 97 patients with depression admitted to our hospital from July 2017 to July 2018 were selected as the study subjects, and 63 health examinees from July 2017 to July 2018 were selected as the control group. Western blot was used to detect the expression of IRE1 alpha and JNK, and the relative value was calculated and analyzed according to OD relative value = target band expression intensity/GAPDH expression intensity. PT-cPCR was used to detect the expression of microRNA-16, microRNA-124 and microRNA-195, and the original CT value was obtained. The average value of three times was taken and the relative value of microRNA was calculated by 2-CT method. Results The relative value of OD expression of IRE1α and JNK in depression group was higher than that in control group (P<0.05). The expression levels of microRNA-16 and microRNA-195 in depression group were lower than those in control group, while the expression levels of microRNA-124 in depression group were higher than those in control group (P<0.05). Conclusion IRE1 α and JNK are highly expressed in the peripheral blood of depressive patients, and the expression levels of microRNA-16 and microRNA-195 are abnormally decreased, while the expression levels of microRNA-124 are abnormally increased. Therefore, it is considered that IRE1 alpha and JNK can be used as biological indicators for diagnosis and evaluation of prognosis of depressive patients.