Due to the low incidence of BRAF mutations, limited data is available about their prevalence and clinical characteristics. Moreover, comparative real-world efficacy of dabrafenib combined with trametinib versus other treatment regimens, especially in Chinese patients, is also lacking.Patients who had BRAF genetic testing from the Lung Cancer Big Data Precise Treatment Collaboration Group (LANDSCAPE) database were included as Cohort I. The LANDSCAPE database comprises next-generation sequencing (NGS) data of 175,336 patients with lung cancer, originating from 6 Chinese genetic testing institutions. Cohort II included patients with unresectable locally advanced or metastatic NSCLC with a primary BRAF mutation from 19 centres in China from December 2015 to September 2022.In Cohort I, of patients with NSCLC, 6249 (3.56%, 95% CI: 3.48%-3.65%) were confirmed to harbour a BRAF mutation. BRAF V600E accounted for 24.6% (1539/6249) of all patients with BRAF-mutated NSCLC. In Cohort II, a total of 129 patients with locally advanced or metastatic BRAF-mutated NSCLC were included. Of 112 patients who received NGS testing, 80 (71.4%) patients had concomitant mutations. The median first-line real-world progression-free survival (rwPFS) of dabrafenib plus trametinib for patients with BRAF V600 mutations was 25.0 months (N = 37), which was numerically longer than first-line immunotherapy-based therapy (N = 12, 15.7 months), and chemotherapy (N = 17, 9.2 months).This study indicates that dabrafenib plus trametinib could be considered as the optimal treatment option for Chinese patients with NSCLC harbouring BRAF V600 mutations.National Natural Science Foundation of China (82072583); Beijing Municipal Administration of Hospitals Incubating Program (PX2020044); Beijing Hospitals Authority Youth Programme (QML20231113); Science Foundation of Peking University Cancer Hospital (2022-17); Peking University Cancer Hospital Inner Mongolia Hospital Public Hospital Reform and High-Quality Development Demonstration Project (Gastrointestinal Cancer + Thoracic Cancer) Research Fund (2024YNYB006).Copyright © 2025. Published by Elsevier B.V.