Background: Evidence-based practice is a technique based on the gathering, interpretation, appraisal, and integration of legitimate, clinically tremendous, and applicable studies. Objective: To assess the knowledge of evidence-based practice and associated factors among nurses working in public hospitals of eastern Ethiopia, 2022. Methods: Institutional-based cross-sectional study design was conducted from June 1-30, 2022. The total sample size was 419 and a simple random sampling technique was used. Data was entered in Epi-data 3.1 and analyzed using Stata version sixteen software. Binary logistic regression was done and all variables with a p-value < 0.25 in bivariable analysis were shifted in multivariable logistic regression analysis. Statistical significance was declared at a p-value < 0.05 in adjusted odds ratio with 95% CI. Result: The good knowledge of evidence-based practice was 59.7% [95%CI: 54.8-64.3]. Sex [AOR 3.26, 95%CI: 1.99-5.34], position [AOR 2.49, 95%CI: 1.23-5.05], administrative help & inspire [AOR 2.04, 95%CI: 1.18-3.54], cooperative and supportive colleagues [AOR 2.38, 95%CI: 1.31-4.32], enhancing research understanding [AOR 2.12, 95%CI: 1.27-3.54], and training [AOR 2.27, 95%CI: 1.36-3.81] have been notably associated with evidence evidencebased practice. Conclusion: About six in 10 nurses had good knowledge of evidence-based practice among nurses working in public hospitals of eastern Ethiopia. Sex, position, administrative help and encouragement, cooperative and supportive colleagues, enhancing research understading, and training have been crucial factors of evidence-based practice among nurses. Consequently, having administrative support and encouragement, working cooperatively and supportive with colleagues, enhancing studies know-how, and gaining good enough schooling might grow the knowledge of evidence-based practice.