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Abstract Background Nursing work is associated with great pressure, and nurses are often overwhelmed. Therefore, correct emotional regulation is essential to improve nurses’ job well-being and promote better engagement in nursing work. The purpose of this study was to establish a structural model to estimate the impact of Chinese clinical nurses’ emotional intelligence on job well-being, using multiple intermediaries to explain the internal mechanisms underlying the relationship. Methods This was a cross-sectional study of 1475 registered nurses from a Chinese hospital who provided responses to emotional intelligence, empathy, communication satisfaction, and job well-being scales. Path analysis using a multiple mediation model was performed using AMOS 23.0. Results Among all clinical nurses who participated in the survey, 1475 (98.33 %) completed the questionnaire. The nurses’ job well-being score was 83.61 ± 12.63. There was a significant positive correlation between job well-being and communication satisfaction, emotional intelligence, and empathy ability (r = 0.346–0.570, P