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Background: We aimed to examine the effectiveness of a nurse-led, screening-triggered early specialized palliative care intervention program for patients with advanced lung cancer., Methods: Patients with advanced lung cancer who underwent initial chemotherapy were randomized to intervention and usual care groups between January 2017 and September 2019. The intervention comprised comprehensive needs assessments, counseling, and service coordination by advanced-level nurses. Patients in the usual care group received the usual oncological care. The primary end point was a change in the trial outcome index (TOI) scores from baseline to 12 weeks. The secondary end-points were TOI scores at week 20, depression, anxiety, and survival., Results: In total, 102 patients were assigned to each group. Compared with the usual care group, no significant improvement in TOI scores was observed at 12 weeks in the intervention group (mean group difference: 2.13; 90% confidence interval: -0.70, 4.95; p = 0.107, one-sided), whereas significant improvement was observed at 20 weeks (3.58; 90% confidence interval: 0.15, 7.00; p = 0.043). There were no significant differences in the change from baseline depression and anxiety between the groups from baseline at week 12 and 20 weeks (depression: p = 0.60 and 0.10, anxiety: p = 0.78 and 0.067). Survival did not significantly differ between the groups (median survival time: 12.1 vs. 11.1 months; p = 0.302)., Conclusions: Nurse-led, screening-triggered, early specialized palliative care did not show significant superiority over usual care during the 12-week study period. However, it may have yielded delayed clinical benefits, such as improved quality of life and this feasible model can be acceptable in clinical practice., Trial Registration: The University Hospital Medical Information Network Clinical Trials Registry: UMIN000025491., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)