Abstract Background Lichen planus (LP) is an inflammatory skin disorder of unknown etiology. Chitinase-3-like protein 1 (YKL-40) is a multifunctional proinflammatory protein, which has an important role not only in immunity and inflammation, but also in the regulation of cell proliferation, differentiation, and apoptosis. Aim of the work The present study was designed to investigate the serum level of YKL-40 in patients with different clinical presentations of LP in comparison to healthy participants in order to study its possible role in the pathogenesis of LP. Patients and methods A total of 60 consecutive subjects were enrolled in this prospective case-control study including 30 patients with different clinical variants of LP (16 male and 14 female patients) in addition to 30 healthy controls matched for age and gender. The serum level of serum YKL-40 was evaluated by means of ELISA method in both patients and controls. Results The serum YKL-40 level was significantly higher (P < 0.001) in patients than in controls. Also, significantly higher levels were found in patients with oral type than in patients with cutaneous type who do not have oral lesions (P < 0.05). The sensitivity and specificity of serum YKL-40 were 62.5 and 81.8%, respectively, (cut off value of 151 pg/ml) for the diagnosis of oral lesions in LP. Conclusion The findings in our study support the role of YKL-40 in the pathogenic process of LP and may help in treatment of lichen planus.