Interstitial lung disease associated with primary Sjögren's syndrome (SJS-ILD) has a variable clinical course. We aimed to investigate the role of blood biomarkers in predicting prognosis for SJS-ILD. Clinical data of 46 SJS-ILD patients were retrospectively reviewed. Plasma biomarker levels, including Krebs von den Lungen-6 (KL-6), CC chemokine ligand 18 (CCL18), chitinase-3-like-1 (YKL-40), interleukin-4 receptor alpha (IL-4Ra), and matrix metalloproteinase-7 (MMP-7) were measured using the multiplex Luminex assays (R&D Systems, Minneapolis, USA). The median follow-up period was 69.0 months. The mean age of the patients was 59.4 years; 17.4% were men. The KL-6 level was significantly higher in non-survivors (n = 12; 119.6 vs. 59.5 pg/mL, P = 0.037) than survivors (n = 34), while the levels of the other biomarkers did not differ. Receiver operating characteristic analysis indicated that KL-6 shows the best performance for predicting survival (area under the curve = 0.705, P = 0.037; best cut-off value = 53.5 pg/mL). Multivariable Cox analysis that was adjusted by age and diffusing capacity for carbon monoxide suggested a high KL-6 level (> 53.5 pg/mL) as an independent prognostic factor for survival (hazard ratio = 5.939, 95% confidence interval 1.312-26.881, P = 0.021). Our results suggest that blood KL-6 might be a useful in predicting the prognosis for patients with SJS-ILD.