A Dust explosion that injured 499 patients occurred on June 27, 2015 in Taiwan. This tragedy inundated hospitals across northern Taiwan with an unprecedented number of burn patients. It caused extreme pressure and challenges for nurses. The purpose of this study is to investigate factors associated with nurses' work stress, resilience, and professional quality of life in caring for dust exposure patients. A cross-sectional survey data was collected from nurses in caring for dust explosion patients. A total of 83 nurses in burn unit, plastic surgery ward, and reconstructive microsurgery unit returned valid data for analysis. Structured questionnaires included demographic inventory, Nurse Stress Checklist, Connor Davidson Resilience Scale, and Professional Quality of Life Scale version 5. The study results showed that work stress deteriorated the professional quality of life, while resilience was a protective factor. Significant positive relationships were observed between work stress, burnout, and secondary traumatic stress. Results of hierarchical regression analysis indicated that resilience helps to ease the deterioration effect of secondary traumatic stress. Results confirm the importance of both work stress and resilience in explaining aspects of professional quality of life. More importantly, resilience was shown as a significant variable impacting level of secondary trauma stress. Intervention in promoting resilience should be targeted in order to reduce secondary trauma among nurses after facing disastrous mass causality incidents.