Objective:To explore the relationship between work stress, sense of coherence (SOC) and compassion fatigue (CF) among oncological nurses, and to study the mediating role of SOC between work stress and CF in oncological nurses.Methods:Totally 370 oncological nurses from 7 ClassⅢ Grade A hospitals in Anhui Province between November 2019 and January 2020 were conveniently selected and investigated with the Chinese Nurse Work Stressor Scale, Sense of Coherence Scale-13, Professional Quality of Life and the general information questionnaire. AMOS 21.0 and SPSS 23.0 were used for statistical analysis of the data. A total of 370 questionnaires were distributed and 345 valid questionnaires were returned.Results:The work stress of oncological nurses was negatively correlated with their SOC ( r=-0.547, P<0.01) , and positively correlated with job burnout and secondary trauma ( r=0.607, 0.418; P<0.01) ; SOC was negatively correlated with job burnout and secondary trauma ( r=-0.581, -0.405; P<0.01) . SOC played a mediating role between the work stress, job burnout and secondary trauma of oncological nurses, and the mediating effect accounted for 45.81% and 33.82% of the total effect, respectively. Conclusions:SOC is a mediating variable between the work stress and CF of oncological nurses. Actively assessing the level of nurses' SOC and providing interventions are helpful to reduce CF caused by work stress.