In conclusion, both in vitro and in vivo experiments confirmed the vital role of DCLK1 in remodeling the EMT program to induce EGFR-TKI-acquired resistance in lung adenocarcinoma, suggesting that DCLK1 is an important regulatory gene that induces the activation of the EMT program, and DCLK1 is a molecule worthy of attention in the event of EGFR-TKI resistance in lung adenocarcinoma. This evidence concerns the gene EGFR and lung adenocarcinoma.