Thus, for the first time, we have described a novel mechanism by which the MEOX2-GLI1 axis is involved in lung cancer malignancy and platinum-based therapy resistance, as well as an association with clinical progression and poor overall survival, in both EGFR-non-mutated and EGFR-mutated lung cancer patients receiving EGFR-tyrosine kinase inhibitor (TKI)-based therapies. Here, GLI1 is linked to lung cancer.