Objective To investigate the relationship between clinical nurses′ empathy, psychological capital, and job burnout, and to provide targeted management suggestions to reduce clinical nurses' job burnout. Methods A total of 1 064 clinical nurses from 1 tertiary hospital and 3 secondary hospitals in Hubei province were recruited to fill out the Interpersonal Reactivity Index, the Psychological Capital Scale and the Maslach Burnout Inventory. Results The scores of nurses′ empathy, psychological capital, emotional exhaustion, depersonalization and personal achievement were (52.95±10.36) points, (91.62±14.50) points, 16.50 (10.00, 25.00) points, 3.00 (1.00, 7.00) points, and (32.31±9.96) points respectively. Hierarchical regression results showed that after controlling for general data, empathy and psychological capital were independent factors of emotional exhaustion and personal accomplishment, accounting for 25.5% and 36.3% of the total variation, respectively. Conclusion Nurses′ job burnout is above the average level, characterized by high emotional exhaustion, low depersonalization, and low personal accomplishment. Nursing managers should provide education and training targeting the main factors, pay attention to nurses′ psychological health, to alleviate the level of job burnout and maintain nursing staff stability.