N6-methyladenosine (m6A) modification has been convincingly identified to be a critical regulator in human cancer. However, the contribution of m6A to NSCLC gefitinib resistance is still largely unknown. Here, we screened and identified that m6A methyltransferase KIAA1429 was highly expressed in gefitinib-resistant NSCLC cells (PC9-GR), tissues, and closely related to unfavorable survival. Functionally, KIAA1429 accelerated the gefitinib resistance of NSCLC in vitro. Depletion of KIAA1429 repressed the tumor growth of PC9-GR cells in vivo. Mechanistically, KIAA1429 enhanced the mRNA stability of HOXA1 through targeting its 3'-untranslated regions (3'-UTR). Overall, our findings indicate that KIAA1429 plays essential oncogenic roles in NSCLC gefitinib resistance, which may provide a feasible therapeutic target for NSCLC.