Objective To explore the relationship between job burnout and innovative behavior of hemodialysis nurses, and to provide reference for targeted interventions. Methods A total of 10 570 nurses from 2 738 hospitals in China were surveyed by a self-designed sociodemographic data questionnaire, the Maslach Burnout Inventory, and Nurse Innovative Behavior Scale. Results The median scores of emotional exhaustion, depersonalization, and low personal accomplishment of hemodialysis nurses were 15, 3 and 28 respectively. The total average score of innovative behavior was 3.08±0.67, and the scores of idea generation, obtaining support and idea realization were 3.56±0.76, 2.76±0.73, and 3.03±0.91 respectively. Innovative behavior was negatively correlated with emotional exhaustion and depersonalization, whereas positively correlated with low personal accomplishment (P<0.01 for all). Multiple linear regression indicated that idea realization was the influencing factor of all dimensions of job burnout (P<0.01 for all). Conclusion Enhancing the innovative behavior of hemodialysis nurses especially idea realization can significantly reduce their job burnout.