Background: Fostering patients' sense of meaning is an essential task for palliative care clinicians. Few studies have reported the effects on nurses of a short-term training program aimed at improving skills to relieve feelings of meaninglessness in terminally ill cancer patients. Objective: The primary aim of this study was to determine the impact on nurses of a novel two-day education program focusing on care that addresses patients' feelings of meaninglessness. Measured were impacts on nurses' confidence, self-reported practice, attitudes toward caring for such patients, burnout, meaning of life, and knowledge. Methods: This study was a randomized controlled trial using the waiting list control. Intervention consisted of a two-day interactive education program. A total of 76 nurses randomly allocated to two groups completed the study. Outcome measures included confidence scale; self-reported practice scale; scales of nursing attitudes toward caring for patients who experience feelings of meaningless (willingness to help, positive appraisal, helplessness, nurse-perceived value of being, and nurse-perceived value of patients' inner power); Maslach burnout scale, Functional Assessment of Chronic Illness Therapy-Spiritual, and knowledge scale. Results: There were significant intervention effects in nurse-reported confidence and nurse-perceived value of patients' inner power. Nurse-reported helplessness showed marginally significant improvement after intervention (p=0.067). No significant intervention effects were observed in the self-reported practice scale; attitudes toward caring for patients (willingness to help, positive appraisal, and nurse-perceived value of being); burnout scale, meaning of life; and knowledge score. The percentages of nurses who evaluated this program as useful or very useful were 95% (understanding the conceptual framework) and 85% (helping to learn how to provide care for patients feeling meaninglessness in clinical practice). Conclusion: This short-term educational intervention had a significant beneficial effect on nurses' confidence and modest effects on attitudes.