Provision of palliative care to patients with advanced chronic diseases or old populations is suboptimal, which results in unnecessary suffering of and burden to patients, caregivers, and society. Low self-efficacy in palliative care among nurses is a factor affecting suboptimal utilization of palliative care. Poor knowledge is a factor affecting low self-efficacy in palliative care of nurses. Attitudes may contribute to the relationship between knowledge and self-efficacy in palliative care, but these relationships have been rarely examined in nurses. This study aimed to determine whether nurses’ attitudes moderate the relationship between knowledge and self-efficacy in palliative care. In a cross-sectional, correlational study, online or offline survey on self-efficacy, knowledge, attitudes, and covariates was conducted from 282 nurses in South Korea. PROCESS v4.1 for SPSS was used to address the study aim. Higher levels of knowledge (p = .048) and attitudes (p < .001), and the interaction term of knowledge and attitudes (p = .025) were significantly associated with higher levels of self-efficacy (F = 6.12, p < .001, R2 = .152), indicating the moderating effects of attitudes. The relationships between higher levels of knowledge and self-efficacy were significant only in nurses with highly and moderately positive attitudes (R2 change = .016, F = 5.11, p = .025), but not nurses with lack of positive attitudes. Our results supported the moderating role of nurses’ attitudes in the relationship between knowledge and self-efficacy. To improve self-efficacy in palliative care in nurses, improvement in knowledge and facilitation of positive attitudes are needed.