BackgroundPostoperative depression is a common complication following non-small cell lung cancer (NSCLC) resection, which adversely affects quality of life and may impede long-term survival. Modified Sini Powder (MSNP), a modified traditional Chinese medicine formula derived from classical Sini Powder, has been used in clinical practice to alleviate depressive symptoms. However, comprehensive evidence from well-designed clinical trials remains insufficient. This protocol describes a study design