〔Abstract〕 Objective To investigate the changes and clinical significance of serum krebs von den lungen-6 (KL-6) in children with systemic lupus erythematosus (SLE) with interstitial lung disease (ILD). Methods 15 children with SLE and ILD who were hospitalized in the Children’s Hospital Affiliated to Soochow University from November 2016 to November 2018 were selected as the SLE-ILD group, and 19 children with SLE-non-ILD were selected as the SLE-non-ILD group. Thirty-two healthy children who were examined in the Children’s Hospital Affiliated to Soochow University were selected as the healthy control group. The serum KL-6 levels of the three groups of children were detected by enzyme-linked immunosorbent assay (ELISA) and compared, and the receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic efficacy of KL-6 for SLE combined with ILD. Results The results of serum KL-6 in the SLE-ILD group, SLE-non-ILD group and healthy control group were 339.14 (320.12, 380.71) U·mL-1, 139.73 (86.86, 190.59) U·mL-1 and 99.43 (76.71, 180.14) U·mL-1 respectively, the SLE-ILD group was significantly higher than that in the SLE-non-ILD group and the healthy control group, the difference was statistically significant (P < 0.05). The area under the ROC curve of KL-6 is 0.907, the best diagnostic threshold is 201.118 U·mL-1, the sensitivity was 0.867 and the specificity was 0.882. Conclusion Serum KL-6 can be used as a biomarker to predict the occurrence of SLE-ILD, and its diagnostic efficiency is high.