Growth factors in the brain are important to depression. We investigated the relationship between serum insulin-like growth factor (IGF-1) and IGF-binding protein-3 (IGFBP-3) concentration and risk of depression and the effect of psychological intervention on outcomes of high-grade glioma patients with preoperative depression. A total of 249 high-grade glioma patients participated in blood sample collection for IGF-1 and IGFBP-3 detection by ELISA and the Hospital Anxiety and Depression Scale testing. The association between IGF-I or IGFBP-3 and depression risk was assessed using conditional logistic regression, and Student's t tests were used to evaluate differences in change of the Karnofsky Performance Status Scale (KPS) in subgroups after performance of psychosocial intervention. The survivals of patients in subgroups were tested by Kaplan-Meier (log-rank test). We found the risk of depression was elevated with increased IGF-I (HR = 6.320, 95 % CI 2.456-16.265, top vs. bottom quartile) and IGFBP-3 concentrations (HR = 3.411, 95 % CI 1.345-8.648) after adjustment of confounders. KPS was increased significantly in the intervention groups, but not significantly in the usual care groups after performance of psychosocial intervention. The survival of depressed patients in the usual group was significantly worse than those of other subgroups after performance of psychosocial intervention. Depression is prevalent among patients with high-grade gliomas, and factors of the IGF axis are positively associated with risk of depression and might be involved in the etiology of depression in high-grade glioma patients. Depression correlates with quality of life and outcomes of patients. Therefore, some psychological interventions are needed and may help patients to relieve depression and improve the life quality of glioma patients.