This study aimed to explore 1) factors that influenced the evidence-based practice competencies and behaviors of clinical nurses and 2) the interaction between the organizational evidence-based practice culture, head nurses' implementation leadership, and nurses' evidence-based practice competencies and behaviors. The significance of organizational evidence-based practice culture and head nurses' implementation leadership in enhancing nurses' evidence-based practice competencies and behavior is widely recognized in healthcare settings. However, there is limited knowledge of how these factors influence nurses' evidence-based practice competencies and behavior. A cross-sectional survey was conducted at 10 hospitals in China. Data were collected via online questionnaires from October to December 2020, utilizing social characteristic questionnaires, the Evidence-Based Practice Questionnaire, the Organizational Culture and Readiness Scale for System-wide Implementation ofEvidence-Based Practice, and the Implementation Leadership Scale. All data were imported into the IBM Statistical Program for the Social Sciences (SPSS) 27.0 and PROCESS version 4.1 macro on SPSS for statistical analysis. The design and reporting of our study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Checklist. We received 1047 (99.15%) valid questionnaires. The multiple linear regression analysis showed that significant factors were organizational evidence-based practice culture, implementation leadership, and years of experience in nursing. After controlling for the impact of the covariate (years of experience in nursing), it was found that organizational evidence-based practice culture partially mediated the relationship between head nurses' implementation leadership and nurses' evidence-based practice competencies and behaviors. Additionally, head nurses' implementation leadership partially mediated the relationship between organizational evidence-based practice culture and nurses' evidence-based practice competencies and behaviors. Organizational evidence-based practice culture, head nurses' implementation leadership, and years of experience in nursing significantly predict nurses' evidence-based practice competencies and behaviors. Organizational evidence-based practice culture and head nurses' implementation leadership mutually mediated their influence on nurses' implementation of evidence-based practice. Head nurses should proactively seek opportunities to enhance their implementation leadership, such as participating in training programs (e.g., mentoring and coaching programs) and attending conferences, workshops, or seminars on implementation leadership. Policymakers should also consider providing more policy support for implementing leadership development and cultivating a positive evidence-based practice culture.