To mimic the naturally occurring BRAF V600E mutation in lung cancer, a BRAF V600E knock-in BEAS-2B cell model was established using CRISPR/Cas9. The proteomics analysis was carried out to evaluate the underlying changes at the proteome level. Proteomics analysis revealed significant changes in the proteins involved in the biological processes including epithelial-mesenchymal transition (EMT), extracellular matrix (ECM)-receptor interaction, cell adhesion, focal adhesion, and cell metabolism upon BRAF V600E mutation.