Targeted therapy has achieved great success in advanced non-small lung cancer (NSCLC) with driver genes, and neoadjuvant-targeted therapy is increasingly being investigated. Although neoadjuvant-targeted therapy with EGFR-TKI and ALK-TKI showed good efficacy, there is no report of neoadjuvant-targeted therapy to BRAF V600E mutation on NSCLC so far. Here, we report the first case of a successful neoadjuvant-targeted therapy with BRAF and MEK inhibitors followed by radical surgical excision with major pathologic response (MPR) in a patient with stage IIIA lung adenocarcinoma (LUAD) harboring BRAF V600E mutation. The case informs us that targeted therapy with BRAF and MEK inhibitors could be administrated as a neoadjuvant strategy for selected cases of NSCLC harboring BRAF V600E mutation.