Objective To investigate the level of Krebs von den Lungen-6 (KL-6) in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD) and analyse its correlation with lung function and inflammatory factors. Methods Totally 98 patients with CTD-ILD admitted from January 2023 to June 2024 were selected as the research subjects. According to GAP staging criteria, the patients were divided into mild group, moderate group and severe group. The differences of serum KL-6, lung function ［forced vital capacity (FVC), forced expiratory volume in one second (FEV1), total lung capacity (TLC), carbon monoxide diffusion capacity (DLCO)］ and inflammatory factors ［erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6)］ were compared among the three groups. Pearson correlation coefficient was used to analyze the correlation between serum KL-6 level at admission and lung function, inflammatory factors levels and disease severity. Receiver operating characteristic curve (ROC) was applied to evaluate the predictive efficiency of KL-6 level, lung function indicators and inflammatory factors in the diagnosis of CTD-ILD. Results 98 CTD-ILD patients were grouped according to the GAP staging criteria, including 29 cases in mild group, 43 cases in moderate group and 26 cases in severe group. The levels of serum KL-6, ESR, CRP and IL-6 in moderate group and severe group were significantly higher than those in mild group (P＜0.05), and the above levels in severe group were higher than those in moderate group (P＜0.05). The FEV1%, FEV1/FVC%, TLC% and DLCO% at admission were lower in moderate and severe groups than those in mild group, and the indicators were lower in severe group than those in moderate group (P＜0.05), the differences were statistically significant (P＜0.05). Pearson correlation analysis showed that serum KL-6 level at admission was positively correlated with ESR, CRP and IL-6 levels in CTD-ILD patients (r=0.248, 0.569, 0.346, P＜0.05), and was negatively correlated with FEV1%, FEV1/FVC%, TLC% and DLCO% (r=-0.427, -0.319, -0.493, -0.622, P＜0.05). ROC curve results indicated that the AUC value of serum KL-6 was higher than that of lung function and inflammatory factors, and it had high sensitivity and specificity. According to the severity of the patients' condition, they were divided into a mild subgroup (n=29) and a moderately severe subgroup (n=69). The results of the ROC curves showed an AUC value of 0.755, a cut-off value of 819.56 (U/mL), a sensitivity of 73.91% and a specificity of 79.31%. Conclusion In patients with CTD-ILD, serum KL-6 level has a strong correlation with lung function and inflammatory indicators, and it is very important for evaluating the disease progression and prognosis of patients with CTD-ILD