<p>Cancer-related fatigue (CRF) is a debilitating symptom affecting patients with lung cancer. While palliative care interventions have shown promise in managing CRF, accessible and scalable solutions remain limited. This study evaluated the efficacy of a WeChat-based palliative care intervention in alleviating CRF among patients with lung cancer. A clinical randomized controlled trial of an 8-week intervention was conducted with 98 lung cancer patients experiencing varying degrees of fatigue. Participants were randomly assigned, with 49 in the intervention group receiving WeChat-based palliative care support, and 49 in the control group receiving usual oncology care. The primary outcome was the change in fatigue severity from baseline to 8 weeks. Between-group differences over time were analyzed using linear mixed models. The intervention group showed significantly greater improvement in total Revised Piper Fatigue Scale (PFS-R) scores. It was indicated by: (1) an overall difference between the intervention and control groups (group, F = 33.04, P &lt; 0.001), (2) changes in scores across time points (time, F = 8.63, P &lt; 0.001), and (3) a group–time interaction, indicating that the intervention group’s improvement over time was greater than that of the control group (F = 11.74, P &lt; 0.001). We found a significant improvement in CRF among patients with lung cancer who received the WeChat-based palliative care program. This demonstrates that the program is an effective intervention for managing CRF and enhancing overall well-being in palliative care settings. The findings provide valuable evidence supporting the integration of eHealth services into clinical and transitional nursing care for individuals living with lung cancer. </p>