Rapid assessment and intervention of suicide risk are common and challenging in psychiatric emergency departments (PED). It is unclear whether distinct pathophysiological processes exist among depressive patients with suicidality. This study examined the network structures of biomarkers on Hypothalamic-Pituitary-Adrenal (HPA) axis, such as Adrenocorticotropic hormone (ACTH) and Corticosterone (Cort), as well as suicidality and depressive symptoms in mood disorder patients in PED. Mood disorder patients in PED were assessed with the measurements of suicidality and depressive symptoms, respectively. A network analysis was performed to identify central symptoms and bridge symptoms of this network and their links to ACTH and Cort. Network stability was examined using the case-dropping procedure. The Network Comparison Test (NCT) was conducted to evaluate whether network characteristics differed by gender. A total of 1815 mood disorder patients were recruited. The prevalence of SI was 31.2% (95% CI: 28.15–34.21%), SP was 30.4% (95% CI: 27.39–33.41%), SA was 30.62% (95% CI: 27.61–33.64%) among psychiatric outpatients. The mean score of HAMD-24 was 13.87 ± 8.02. Network analysis revealed that ‘Somatic anxiety’ had the highest expected centrality, followed by ‘Hopelessness’ and ‘Suicide attempt’. ‘Corticosterone’ and ‘Retardation’ may be the main bridge symptoms between depressive symptoms and the suicidality community. The network model showed a high degree of stability. Gender did not significantly influence the network structure. The central symptoms and key bridge symptoms identified could be potential targets for interventions of the HPA axis, which is designed for regular screening of a range of suicidal activity. In the light of this, timely treatment should be provided for psychiatric emergency care.