Objective: Interstitial lung disease (ILD) is one of the most severe complications which is associated with connective tissue disease (CTD) and causes to morbidity and mortality. So, we aimed to determine serum levels of interleukin-6 (IL-6), IL-13, and IL-17, to investigate whether these cytokines are related to CTD-ILD, and to find their possible contribution to determining the prognosis of the disease. Methods: A total of 150 participants, 80 patients diagnosed with CTD-ILD (mean age, 58.21 ± 12.36) and 70 healthy controls (mean age, 57.07 ± 9.60) were recruited from the rheumatology department between January 2016 and June 2019 in the study. High-resolution computed tomography (HRCT) findings were scored as similarly to previous studies. Serum IL-6, IL 13, and IL-17 levels were measured by ELISA test kits. Results: The levels of IL-6, IL-13, and IL-17 in CTD patients were significantly higher than the healthy individuals (p < 001), but the HRCT score’s relation were not determined. IL-6 was associated with disease duration and disease activity scores of DAS28, ESDAII, and dSSc. There was a significant relation between dSSc, HCRT fibrosis, and total score.CRP, hemoglobin, and platelets were associated with the HRCT inflammation pattern. Conclusion: At the study, it has been observed that serum IL-13, IL-6 and IL-17 levels are increased in patients with CTD-ILD. Besides, IL-6 was associated with disease activity scores of DAS28, ESDAII, and dSSc. Also, HRCT fibrosis score is associated with dSSc. Further and comprehensive studies are needed to understand better the complex intersection of lung disease with systemic autoimmunity.Key Points•Serum IL-13, IL-6, and IL-17 levels are increased in patients with CTD-ILD.•IL-6 was associated with disease activity scores of DAS28, ESDAII, and diffuse skin involvement.•HRCT fibrosis score is associated with diffuse skin involvement in patients with SSc-ILD.•HRCT inflammation score is associated with PAH.