Background: The medical burden of psychiatric disorders continues to increase and has caused a major impact on health, society, human rights, and economy in the world. Patients with mental illness have a higher ratio of emergency department visits than non-psychiatric patients. Psychiatric disorder-related emergency department care is a stress-causing factor in emergency department work. Therefore, the purpose of this study was to explore the experience of emergency department nurses in caring for patients with mental illness. Methods: A descriptive qualitative research design with purposive sampling was adopted. A total of 17 nurses working in the emergency department in central Taiwan were recruited. In-depth semi-structured interviews were conducted and thematic content analysis was performed. Results: Four themes and six sub-themes emerged that described the experiences of emergency nurse caring for patients with mental illness: (1) Mindset; (2) The predicament of psychiatric care: Violence and isolation and helplessness, and lack of therapeutic communication skills; (3) The influence of open space: insufficient safety and privacy; and (4) The educational needs of psychiatric nursing: improving cognition in psychiatric patients and changing negative thinking into positive thinking. Conclusions: The results revealed the experience of emergency nurses in caring for patients with mental illness. Emergency psychiatric nursing training related to foundational psychiatric knowledge, communication skill, concept of recovery, coping with violence restraining are needed for nurses who work in emergency departments.