Lung cancer is a leading cause of cancer mortality, with non-small cell lung cancer (NSCLC) comprising the majority of cases. Despite the advent of immune checkpoint inhibitors (ICIs), a significant number of patients fail to achieve a durable response, highlighting the need to understand the factors influencing treatment efficacy. Saliva samples and tumor samples were collected from 20 NSCLC patients. The salivary microbiota was profiled using metagenomic next-generation sequencing, and metabolites were analyzed via liquid chromatography-mass spectrometry to identify correlations among bacteria, metabolites, and immunotherapy responses. Immunohistochemistry (IHC) analysis of tissue samples verified the result. Besides,