Burnout is highly prevalent among nurses; however, the effect of personalized music intervention on burnout remains unclear on nurses. We aimed to investigate the effects of personalized music intervention in relieving burnout among nurses. Fortytwo eligible nurses were recruited for an assessor-blinded, two-arm parallel randomized controlled trial. The participants were randomly assigned to the following two groups: The personalized music group (n = 21), which listened to music of their choice for 30 min per session three times per week for 5 weeks; and the waitlist control group (n = 21), which did not listen to any music for relaxation. At baseline, nurses in the personalized music group had worse emotional exhaustion and greater depression compared with the wait-list control group. Results from an analysis of covariance using baseline emotional exhaustion and depression as covariates indicated that nurses who received personalized music intervention experienced less emotional exhaustion than the nurses in the wait-list control experienced. Personalized music intervention can be used for nurses as an adjuvant approach to reduce emotional exhaustion and then improve their well-being.