Purpose: Interstitial lung disease (ILD) damages the lungs and can be caused by environmental exposures and collagen-vascular diseases. The systemic immune-inflammation index (SII) is investigated to diagnose and manage ILDs in different etiological diseases. The study aims to examine the usefulness of SII in diagnosing specific ILDs like Sjogren's syndrome (SjS)-ILD, interstitial pneumonia with autoimmune features (IPAF), and idiopathic pulmonary fibrosis (IPF). Materials and methods: In this cross-sectional study, we included 109 patients with IPAF, IPF, and SjS-ILD. Demographic characteristics, symptoms, lung patterns, autoantibodies, and SII were assessed. Morphologic, serologic, and clinical factors determined the classification of IPAF. Student's t-test, Mann-Whitney U test, PearsonSpearman's method, and receiver operating characteristic (ROC) curves were used to analyze data. Results: Male patients were more common in IPF and IPAF, while SjS-ILD had mostly female patients. Raynaud's phenomenon and dry mouth/eyes were more common in SjS-ILD compared to IPF and IPAF. The groups had significant differences in patterns, antinuclear antibody positivity, and SII levels. SII levels differed significantly between IPAF, SjS-ILD, and IPF patients, and were correlated with CRP in IPAF and SjS-ILD. The cut-off value of the SII between IPAF and IPF in patients with ILD was 576.1 with 76.0 % sensitivity and 76.0 % specificity. Conclusions: Evaluation of SII provides valuable information for understanding and identifying different disease groups with ILDs.