Lycii Radicis Cortex (LRC) is a medicinal and food homologous plant with various pharmacological activities, including anti-tumor effects. This study explores the anti-tumor effect of LRC on non-small cell lung cancer (NSCLC) and its molecular mechanism using mice bearing Lewis lung carcinoma cells. LRC significantly suppressed the growth of NSCLC. Besides, RNA sequencing of mice tumors and hematoxylin & eosin and immunofluorescence staining revealed that LRC promoted the infiltration of T lymphocytes, specifically GZMB⁺CD8⁺T lymphocytes, in tumor tissues. The Gene Set Enrichment Analysis of spleen RNA indicated that LRC up-regulated PD-1-downstream pathways, suggesting that LRC exerted its effects through the PD-L1/PD-1 pathway. Further experiments revealed that LRC interacted with PD-L1, blocking PD-L1/PD-1 binding and thus restoring the T cell killing activity on tumor cells. Together, these results support using LRC as healthy food to improve anti-tumor immunity in patients with NSCLC.