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With the continuous development of immunotherapy, the treatment of patients with advanced non-small cell lung cancer (NSCLC) is gradually becoming more and more precise. The clinical benefit of immune checkpoint inhibitors in patients with NSCLC with positive programmed cell death-ligand 1 (PD-L1) expression is obvious, but the effect in patients with negative expression remains inexact. This article reviews the treatment options available for advanced NSCLC patients with negative PD-L1 expression, aiming at providing references and options for their treatment.