Background <p>Cancer cases are increasing every day, which makes oncology nursing education very important. Nursing students need to learn how to manage the many symptoms caused by cancer and its treatments. This study aimed to examine the effect of a cooperative learning approach with concept maps on nursing students’ knowledge acquisition on symptom management in cancer patients.</p> Methods <p>This study was a pre-test post-test open-label, randomized controlled design. The study sample consisted of 90&#xa0;s-year nursing students randomized into experimental (<i>n</i> = 45) and control (<i>n</i> = 45) groups. Symptom management training was implemented with the experimental group students using a cooperative learning approach with concept maps. Standard training was maintained with the control group students. The study data were collected using the “Personal Information Form”, “Knowledge Test on Symptom Management in Cancer Patients”, and “Self-Directed Learning Scale”.</p> Results <p>According to repeated-measures ANCOVA analyses adjusted for baseline scores, a significant time effect was observed in the intervention group (F = 13.24, <i>p</i> = 0.001). After adjustment, the intervention group achieved higher adjusted post-test and follow-up knowledge scores compared with the control group. In addition, ANCOVA results for self-directed learning ability demonstrated a strong group effect on post-test scores (F(1,87) = 97.75, <i>p</i> &lt; 0.001, partial η² = 0.529), with higher adjusted mean scores in the intervention group.</p> Conclusions <p>This study concluded that the cooperative learning approach using concept mapping for symptom management in cancer patients is effective in increasing nursing students’ knowledge levels and knowledge retention, as well as in developing self-directed learning.</p> Trial registration <p>Clinical trial number: NCT06695702, date of the registration: November 11, 2024.</p>