Objective To explore the mediating effect of perceived holistic humanistic care between compassion fatigue and work engagement of nurses,and to provide reference for alleviating nurses′ compassion fatigue and enhancing nurses′ work engagement. Methods Using the convenience sampling method，a total of 240 clinical nurses from 12 tertiary Grade A hospitals in China were selected as the survey objects from April 1st to 30th, 2024. A survey was conducted using a general information questionnaire, the Professional Quality of Life Scale5(ProQOL5)，the Holistic Human Caring Perception Scale and the Utrecht Work Engagement Scale(UWES). Spearman correlation analysis was used to test the correlation between perceived holistic humanistic care、compassion fatigue and work engagement. AMOS 29.0 software was used to establish a structural equation model and verify the mediating effect. Results Effectively surveyed 225 nurses,the total score of UWES was 68.00（46.00，89.00） points,the total score of compassion fatigue was 59.00（42.50，79.00）points，the total score of Holistic Human Caring Perception Scale was 81.00（44.00，118.00）points. Compassion fatigue was negatively correlated with work engagement and perceived holistic humanistic care, perceived holistic humanistic care was positively correlated with work engagement（all P＜0.05）. Perceived holistic humanistic care played a partial mediating role between compassion fatigue and work engagement，with the mediating effect accounting for 23.196% of the total effect. Conclusions The work engagement of clinical nurses from tertiary Grade A hospitals is in the medium level,compassion fatigue is in the medium level，perceived holistic humanistic care is in the low level. Compassion fatigue can affect work engagement through the mediating effect of perceived holistic humanistic care, indicating that medical institutions can improve nurses′ work engagement by alleviating compassion fatigue and utilizing the mediating effect of perceived holistic humanistic care.