To investigate the characteristics of nurses' empathy and explore the correlation between nurses' empathy and personality, a cross-sectional study with 250 nurses from a general hospital in China was conducted using the Chinese Big Five Personality Inventory (CBF-PI) and the Jefferson Scale of Empathy–Health Professionals (JSE-HP). The total score of the JSE-HP was 110.60 (SD = 11.71). Employment forms and child-rearing situations were the significant predictors of the JSE-HP score. Multiple hierarchical regression analysis indicated that the JSE-HP score was positively correlated with conscientiousness and agreeableness and the contribution of CBF-PI to JSE-HP scale variances was 15.1%. The results demonstrated that nurses' empathy is on the high level. The Big Five Personality model is a significant predictor of nurses' empathy. The findings of the study provide reference for nurses' humanistic care training and education. In addition, training programs emphasizing emotions, psychology, humanistic quality, and healthy personality should be strengthened to promote nurses' empathy.