Objective:To explore the mediating effect of perceived professional benefits between the humanistic literacy and spiritual care competence among oncology nurses.Methods:From September to October 2022, convenience sampling was used to select 354 oncology nurses from 11 ClassⅢ Grade A hospitals in Sichuan Province, Guangdong Province, and Hubei Province as the research subject. A survey was conducted on oncology nurses using the General Information Questionnaire, Nurses' Perceived Professional Benefit Questionnaire, Nurses' Humanistic Literacy Scale, and the Chinese version of the Spiritual Care Competence Scale (SCCS) . Pearson correlation was used to analyze the relationship between nurses' humanistic literacy, perceived professional benefits, and spiritual care competence. AMOS 26.0 software was used to analyze mediating effects. A total of 354 questionnaires were distributed, and after excluding 7 unqualified questionnaires, 347 valid questionnaires were collected, with a valid response rate of 98.02%.Results:Among 347 oncology nurses, the score of the Chinese version of SCCS was (77.60±19.04) . The total score of the SCCS was positively correlated with the total scores of the Nurses' Humanistic Literacy Scale, the Nurses' Perceived Professional Benefit Questionnaire, and scores of all dimensions, with statistically significant differences ( P<0.01) . Bootstrap test showed that the mediating effect of perceived professional benefits among oncology nurses between humanistic literacy and spiritual care competence was 0.284 [95% CI (0.408, 0.860) ] , accounting for 50.90% of the total effect. Conclusions:The perceived professional benefits of oncology nurses play a partial mediating role between humanistic literacy and spiritual care competence. We should strengthen training on the humanistic literacy of oncology nurses, enhance their perceived professional benefits, form a virtuous cycle of employment, and thereby improve their spiritual care competence.