Introduction: This study aims to assess the palliative care nursing (PCN) knowledge and attitude of nursing students toward end-of-life care (EoLC) after completing the multi-methods PCN courses. Methods: A quasi-experimental study with a pre-and post-palliative survey was conducted. One hundred and sixty five nursing students from a faculty of nursing in Indonesia were enrolled, and knowledge and attitude were assessed using the palliative care quiz for nurses (PCQN) and the Frommelt Attitude Toward Care of the Dying and Death (FATCOD). Paired t-test and ANOVA were applied in this study. Results: After being involved in the PCN course, the mean score of PCN knowledge of the students increased significantly (p < 0.001). According to sub-domain analysis, the knowledge increased significantly in pain and symptom management (p < 0.001) and not significantly in the domains of theory and principle of the palliative, psychosocial, and spiritual care (p = 0.053; p = 0.080). Moreover, students’ attitude toward EoLC also increased significantly (p < 0.001), and positive attitudes increased from 75.6% to 91.5%. According to the ANOVA test, knowledge in two different groups (witnessed dying people and GPA) is not statistically meaningful (FWDP (1158) = 0.817, p = 0.367; FGPA (2.158) = 1.143, p = 0.322). Similarly, attitudes toward EoLC in two different groups are not statistically meaningful (FWD (1158) = 0.971. p = 0.326, FGPA (1157) = 1.278, p = 0.281). Conclusion: PCN courses with multi-method learning and teaching are effective to increase PCN knowledge, particularly in pain and symptom management knowledge, and also effective in increasing the positive attitudes toward EoLC.