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Aim: Acute skin failure (ASF) can happen in critically ill patients. Therefore, adequate knowledge and skills regarding ASF are essential to manage this disorder. The aim of this work was to investigate the nurses' knowledge, attitude, and practice (KAP) regarding ASF patients and to analyze its influencing factors in the intensive care unit. Methods: A multicenter cross‐sectional study was performed in 10 tertiary hospitals in March 2022. Eligible nurses received a survey with a self‐designed questionnaire about their KAP regarding ASF, which included three dimensions and a maximum score of 120. A higher score corresponded to better KAP. Results: A total of 255 nurses participated in this study. The mean KAP score was 75.6 ± 16.9. The mean scores of the knowledge, attitude, and practice dimensions were 26.2 ± 10.6, 38.2 ± 6.1, and 11.3 ± 4.3, respectively. The dimensions were ranked according to score (from low to high) as follows: knowledge (2.6 ± 1.1), practice (2.8 ± 1.1), and attitude (3.8 ± 0.6). Multivariate linear regression analysis showed that more training sessions and an advanced professional title were associated with higher KAP scores. Conclusions: The overall KAP score on ASF was low in nurses. Nurses had a positive attitude towards ASF, but their knowledge and practice required significant improvement. Those who had received more training and held a more advanced professional title exhibited higher KAP scores regarding ASF. Therefore, nurse managers should establish a relevant knowledge training system, strengthen relevant training, and improve nursing practices for ASF in order to achieve a high level of KAP in nurses who treat ASF patients. [ABSTRACT FROM AUTHOR]