This study evaluates the usefulness of serum KL-6, SP-D and TGF-β1 levels in assessing lung impairment and predicting interstitial lung disease (ILD) short-term progression in patients with interstitial pneumonia with autoimmune features (IPAF). A total of 24 patients with IPAF, 21 with connective tissue disease-associated ILD (CTD-ILD) and 23 with CTD without ILD were followed for 1 year. Serum levels of KL-6, SP-D and TGF-β1 were measured and their associations with disease severity and progression were analysed. KL-6, SP-D and TGF-β1 levels were significantly higher in IPAF and CTD-ILD patients compared to CTD without ILD ( < 0.0001, = 0.0005 and = 0.0001, respectively). KL-6 (r = 0.45, = 0.002) and SP-D (r = 0.35, = 0.02) levels correlated with lung involvement in HRCT in the ILD group. In IPAF, KL-6 levels correlated with pulmonary function tests (FVC%, TLCO%, and 6MWD) and SpO2, while SP-D correlated with 6MWD and SpO2. In CTD-ILD, KL-6 and SP-D levels were positively correlated with BAL cell count (KL-6: r = 0.58, = 0.04; SP-D: r = 0.63, and = 0.02). KL-6 also showed a negative correlation with the time since symptom onset (r = -0.51, = 0.02). No significant associations were found between the baseline biomarker levels and ILD progression risk. KL-6 and SP-D may serve as potential biomarkers for assessing lung impairment in IPAF, though their predictive value for short-term prognosis remains uncertain.