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Emotional labor is common in nursing but may be affected by the mental state of nurses. This study explored the effect of compassion fatigue on emotional labor and whether self-compassion moderates this effect of compassion fatigue. Methods: A two-stage survey design with a convenience sample. Participants were female nursing staff recruited from emergency departments, intensive care units, ward nursing units, and outpatient departments of medical centers, regional hospitals, and district hospitals in Taiwan. A total of 300 questionnaire copies in each of the first and second stages were distributed, and 272 pairs of responses were retrieved (valid response rate = 91%). The reliability and validity of the questionnaire were tested, and confirmatory factor analysis was conducted with AMOS 21. The proposed hypotheses were verified using hierarchical regression conducted with SPSS version 25.0. Results: This study revealed that compassion fatigue positively predicted surface acting (β = 0.12, p < 0.05) and negatively predicted deep acting (β = −0.18, p < 0.01) and expression of genuine emotions (β = −0.31, p < 0.01). In addition, self-compassion negatively moderates the relationships between compassion fatigue and surface acting (β = −0.12, p < 0.05), and positively moderates the relationships between compassion fatigue and expression of genuine emotions (β = 0.15, p < 0.01). Conclusions: To avoid excessive consumption of emotional resources, nurses with high compassion fatigue may employ surface acting by engaging in emotional labor without making an effort to adjust their feelings. Nurses need also be sympathized with, and such sympathy can come from hospitals, supervisors, colleagues, and, most crucially, the nurses themselves. Hospital executives should propose improvement strategies that can prevent the compassion fatigue on nurses, such as improving nurses’ self-compassion.