Collectively, the major findings of this work are as follows: i) AKR1C1 confers resistance to gefitinib in EGFR-mutated NSCLC; ii) the pharmacological targeting of AKR1C1 with ALA has a strong synergism with gefitinib; and iii) STAT3 may dictate AKR1C1-mediated gefitinib resistance (Fig. S7). This evidence concerns the gene EGFR and non-small cell lung carcinoma.