8555 Background: To compare the efficacy and safety of drug-eluting bead bronchial arterial chemoembolization (DEB-BACE) combined with intravenous chemotherapy versus systemic intravenous chemotherapy for intermediate to advanced lung adenocarcinoma with positive driver genes after progression of targeted therapy. Methods: A total of 131 patients with intermediate to advanced lung adenocarcinoma were retrospectively recruited from 2018-2022 and divided into Group A (standard chemotherapy regimen, N=62) and Group B (DEB-BACE and intravenous chemotherapy, N=69). The short-term efficacy, hemoptysis remission rate, dyspnea remission rate, and incidence of adverse effects were compared between the two groups using the χ2 test. Survival estimates were performed by Kaplan-Meier, and a Log-rank test was performed to examine survival differences between groups. Results: The three-month disease control rate (DCR: 82.6% vs 58.1%) and objective remission rate (ORR: 60.9% vs 38.7%) were better in group B than in group A (both P<0.05). Median progression-free survival (PFS, 10.0 vs 7.9 months) and median overall survival (OS, 33.0 vs 18.0 months) were better in group B than in group A (both P < 0.05). The PFS rates at 6, 12, and 24 months were 67.3%, 40.8%, and 0.0% and 54.1%, 23.2%, and 0.0% in groups B and A, respectively; and the OS rates at 6, 12, and 24 months were 100%, 95.7%, 72%, 88.6%, 66.1%, and 21.8% in group B and group A, respectively, with statistically significant differences (P < 0.05). Within one month after treatment, group B had better hemoptysis relief (83.3% vs. 20.0%) and dyspnea relief (57.5% vs. 30.0%) than group A (both P < 0.05). During the follow-up period, the incidence of adverse reactions was significantly lower in group B than in group A (P < 0.05). Conclusions: For patients with intermediate to advanced lung adenocarcinoma who have failed to progress on targeted therapy, DEB-BACE combined with intravenous chemotherapy has shown superior efficacy and survival benefit and lower adverse effects, while significantly improving patients' symptoms of hemoptysis and dyspnea, with important application prospects.