To investigate the clinical significance of leukocyte-to-lymphocyte ratios, particularly the eosinophil-to-lymphocyte ratio (ELR) and basophil-to-lymphocyte ratio (BLR), in IgG4-related disease (IgG4-RD). We enrolled 541 treatment-na & iuml;ve IgG4-RD patients and compared their ELR, BLR, neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR) with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sj & ouml;gren's syndrome (pSS) patients. K-means cluster analysis was performed to categorize enrolled IgG4-RD patients based on inflammatory markers (ELR, BLR, NLR, Complement 3, Complement 4, erythrocyte sedimentation rate), and clinical data of different clusters were analyzed using statistical methods including Kaplan-Meier curves and Cox regression. ELR and BLR levels were significantly elevated in IgG4-RD patients (ELR: 0.11 [0.05-0.22]; BLR: 0.02 [0.01-0.03]) compared to SLE, RA, and pSS patients (all P < 0.001). ELR was strongly associated with higher disease activity, increased serum IgG4, the number of affected organs, and proliferative phenotype proportions in IgG4-RD patients. We identified a high-risk subgroup of IgG4-RD patients with high ELR/BLR and low complement 3/4 (C3/C4) through clustering analysis. This subgroup exhibited higher disease activity and relapse risk. And IgG4-RD patients with high ELR (>= 0.1103) had higher relapse rates during follow-up (HR = 2.12, 95% CI 1.37-3.26, P = 0.0005). ELR was identified as a risk factor for relapse in IgG4-RD patients. Our study indicated that the significantly elevated ELR reflects Th2 immune dysregulation and disease severity in IgG4-RD and serves as an independent predictor of relapse, offering a potential biomarker for personalized management.