BACKGROUND: Bulky tumor (T ≥ 50 mm) significantly compromises treatment outcomes in advanced non-small cell lung cancer (NSCLC) due to excessive tumor burden. Bronchial arterial chemoembolization (BACE) serves as an effective local intervention for reducing tumor size. The combination of immunotherapy and BACE has shown promising efficacy and an acceptable safety profile. However, the effectiveness of this combined regimen in patients with bulky tumors has not been thoroughly investigated. METHODS: We conducted a retrospective analysis of 68 patients with advanced NSCLC (IIIB-IVB) who suffered from bulky tumors. Based on first-line treatment, patients were divided into two groups: those who received tislelizumab plus BACE followed by tislelizumab and systemic chemotherapy (Group A, n=34), and those who received tislelizumab plus chemotherapy alone (Group B, n=34). Outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Prognostic factors for PFS were identified using univariate and multivariate Cox regression analyses. RESULT: The ORR was significantly higher in Group A than in Group B (79.41% [27/34] vs 44.12% [15/34], p = 0.006). A significant improvement in median progression-free survival (PFS) was observed in Group A relative to Group B (12.47 months vs 7.73 months, HR: 0.55, 95% CI: 0.30-0.99, p = 0.024). There was no statistically significant difference in median OS between the two groups (20.73 months vs 19.63 months, HR: 0.64, 95% CI: 0.31-1.31, p = 0.071). Multivariate analysis identified the sequential treatment strategy (HR: 2.1, 95% CI:1.13-3.904, p = 0.019) and tumor diameter (HR: 2.263, 95% CI:1.077-4.755, p = 0.031) as independent favorable predictors of PFS. The most frequent grade 3 or higher treatment-related adverse events (TRAEs) included neutropenia (17.65% in group A vs 14.71% in group B), anemia (11.76% vs 17.65%, respectively), and thrombocytopenia (14.71% vs 17.65%, respectively). Regarding BACE-related adverse events, chest pain was reported in one patient (2.94%) in group A, and treatment-related transient cough occurred in four patients (11.76%), all of which were grade 1. CONCLUSION: In our cohort of patients with bulky tumors, this sequential strategy was associated with a favorable objective response rate and prolonged median progression-free survival, while maintaining a manageable safety profile.