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The aim of this study was to evaluate the efficacy of hypotonic 0.18% sodium hyaluronate (SH) eye drops under the clinical settings of the dry eye workshop treatment guideline for mild dry eye disease (DED).This analysis included 60 patients with DED. Patients with level 1 DED were treated with either isotonic 0.1% SH (group 1) or with hypotonic 0.18% SH eye drops (group 2). Patients with level 2 DED were treated with 0.1% fluorometholone, 0.05% cyclosporine A, and either isotonic 0.1% SH (group 3) or hypotonic 0.18% SH (group 4) eye drops. Tear film breakup time (TBUT), Schirmer test, corneal staining with fluorescein, and ocular surface disease index score were recorded at baseline, 1 month, and 3 months after treatment.In group 2, TBUT at 3 months (P = 0.03) and corneal staining scores at 1 and 3 months (P ≤ 0.03) were significantly improved after the treatment compared with baseline scores, whereas these parameters were not changed during the follow-up period in group 1. In groups 3 and 4, TBUT and corneal staining scores at 1 and 3 months, and ocular surface disease index score and Schirmer test results at 3 months after the treatment showed significant improvements compared with the baseline score (P < 0.05). Group 4 patients showed an extended TBUT and an improved corneal staining score (P ≤ 0.01) at 3 months after treatment, compared with the values of group 3.Hypotonic 0.18% SH eye drops seemed to be effective in improving tear film stability and ocular surface integrity compared with isotonic 0.1% SH eye drops in patients with mild DED.