Objective To explore the correlation between depression and systemic immune inflammation index (SII) in maintenance hemodialysis (MHD) patients. Methods MHD patients who underwent regular dialysis in the hemodialysis room of Beijing Integrated Traditional Chinese and Western Medicine Hospital from February 2023 to June 2023 were selected. Based on the Hospital Anxiety and Depression Scale (HADS) score, the patients were divided into a non depression group and a depression group. Independent risk factors for depression in MHD patients were analyzed through inter group comparison, univariate, and multivariate logistic regression analysis, and the predictive value of SII on depression symptoms in MHD patients was evaluated by subject work characteristic curve (ROC). Results Among 73 MHD patients included, 32 were in a depressive state (43.84%). The comparison between groups showed that the body mass index (BMI), platelet count, albumin (P＜0.01), and SII (P＜0.001) in the depressive group were significantly higher than those in the non depressive group, while total cholesterol (TC), education years, and low density lipoprotein cholesterol (LDL-C) (P＜0.05) were significantly lower than those in the non depressive group. Multivariate logistic regression showed that the quartile of SII was an independent risk factor for depression in MHD patients. Among them, MHD patients with SII between 692.82 and 1128.6 had a depression risk 8.346 times that of SII ≤ 542.5 (P＜0.05), and MHD patients with SII ＞1128.6 had a depression risk 33.643 times that of SII ≤542.5 (P＜0.01). ROC curve analysis of SII can predict the occurrence of depression in MHD patients, with AUC of 0.768 and diagnostic threshold of ＞774.53 (P＜0.001).Conclusion Compared with non depressive MHD patients, depressive patients have stronger inflammation and poorer immune function. High SII is an independent risk factor for depression in MHD patients and an ideal inflammatory marker for predicting and identifying depression in MHD patients