BACKGROUND: Immune checkpoint inhibitors (ICIs) have left a deep impression in the treatment of non-small cell lung cancer (NSCLC), however, not all patients benefit from it. The purpose of this study was to investigate the prognostic value of baseline bone mineral density (BMD) derived from chest computed tomography (CT) scans in NSCLC patients treated with ICIs. METHODS: This study included patients with advanced NSCLC who underwent ICI treatment at the Wuhan Union Hospital from March 2020 to October 2022. Baseline BMD was evaluated at non-contrast chest CT at the level of first lumbar vertebra. Patients were divided into BMD-lower group and BMD-higher group according to the optimal cutoff value calculated by X-tile software. Baseline characteristics of the two groups were compared and variables between the two groups were balanced by propensity score matching (PSM) analysis. We calculated the objective response rate (ORR) and disease control rate (DCR) of the two groups and analyzed overall survival (OS) and progression-free survival (PFS) using BMD and other clinical indexes through Cox regression models and Kaplan-Meier survival curves. RESULTS: A total of 479 patients were included in this study, and all patients were divided into BMD-lower group (n=270) and BMD-higher group (n=209). After PSM analysis, each group consisted of 150 patients. ORR (43.3% vs. 43.5% before PSM, = 0.964; 44.7% vs. 44.7% after PSM, = 1.000) and DCR (91.1% vs. 94.3% before PSM, = 0.195; 93.3% vs. 96.7% after PSM, =0.190) were similar in two groups. There was no statistically significant relationship between BMD degree and PFS before (16.0 months vs. 18.0 months, = 0.067) and after PSM analysis (17.0 months vs. 19.0 months, = 0.095). However, lower BMD was associated with shorter OS both before (20.5 months vs. 23.0 months, < 0.001) and after PSM analysis (20.0 months vs. 23.0 months, = 0.008). CONCLUSION: Lower baseline BMD is associated with worse clinical outcomes in NSCLC patients treated with ICIs. As a reliable and easily obtained individual prognostic biomarker, BMD can become a routine detection indicator before immunotherapy.