Objective We aimed to investigate the clinical value of checking serum chitinase-3-like-1 protein (YKL-40) levels in anti-MDA5 antibody-positive dermatomyositis (anti-MDA5(+)DM) patients. Methods One hundred and five consecutive anti-MDA5(+)DM patients and 44 healthy controls were enrolled in this study. Baseline and follow-up serum YKL-40 were detected by ELISA. We evaluated the association of YKL-40 with rapidly progressive interstitial lung disease (RPILD), severity of interstitial lung disease (ILD), and ILD-related survival. Results Forty-one out of 105 anti-MDA5(+)DM patients had RPILD at the time of serum sample collection (39.0%). Serum YKL-40 levels were significantly higher in anti-MDA5(+)DM patients with RPILD compared with those without (p=0.011). One month after treatment, patients with aggravated ILD had increased YKL-40 levels, while those with stable/improved ILD had decreased YKL-40 levels. Higher serum levels of ferritin and YKL-40, as well as lower peripheral CD3(+)T cell counts, were independently associated with poorer prognosis. Kaplan-Meier survival curve showed that the 6months survival rate in patients with high serum YKL-40 level (>80ng/ml) was significantly lower than that in patients with low YKL-40 level (<= 80ng/ml) (67% vs 89%, p<0.01). Conclusion YKL-40 can be useful as an indicator for the occurrence of RPILD and correlates with severity of ILD and poor prognosis in anti-MDA5(+)DM patients. Closely monitoring and intensive treatment are suggested in anti-MDA5(+)DM patients showing high level of YKL-40, especially levels >80ng/ml.