【Abstract 】Objective To investigate the clinical efficacy and safety of cyproterone combined with sodium hyaluronate in the treatment of moderate to severe dry eye. Methods 112 patients (224 eyes) underwent moderate to severe dry eye disease were selected as subjects admitted to our hospital from August 2013 to September 2016. The patients were divided into observation group and control group according to the random number table method, each group of 56 cases (112 eyes). The control group was treated with sodium hyaluronate eye drops, each time 1 drop, 3 times a day. The observation group was combined with clopidogrel eye drops on the basis of the control group, each time 1 drop, 3 times a day. Two groups of patients were treated for 4 courses, 2 weeks for a course of treatment. The clinical data of the selected patients were retrospectively analyzed. The corneal fluorescein staining score (FL), tear film rupture time (BUT), dry eye symptom score and tear secretion test (SchirmerⅠ) were observed before and after treatment in two groups. Its clinical efficacy and safety were analyzed. Results No significant difference of dry eye symptom score, BUT and FL score was detected between the observation group and the control group before and after treatment (P>0.05). The dry eye symptom score, BUT and FL score of observation group before treatment were significantly improved compared with that after treatment for 1, 2, 3 and 4 courses (P＜0.05). The difference of dry eye symptom score, BUT and FL score after treatment between observation group and control group was statistically significant (P＜0.05). The results of Schirmer I of observation group and the control group before treatment had no significant difference (P>0.05). No significant difference of Schirmer I was detected between the observation group and the control group after 1, 2 courses of treatment (P>.0.05); After 3, 4 courses of treatment, the observation group was significantly improved compared with before treatment, the difference of Schirmer I was statistically significant (P＜0.05). The total effective rate of observation group and control group were 98.21% and 83.93%. The difference of clinical efficacy of the two groups was statistically significant (P＜0.05). The incidence of adverse reactions in the observation group and the control group were 5.36% and 7.14%. No significant difference was detected in the incidence of adverse reactions between the two groups (P>.0.05). Conclusion Clopidopine combined with sodium hyaluronate has a better clinical effect in the treatment of moderate to severe dry eye disease. It can significantly improve the clinical symptoms, reduce the incidence of adverse reactions, shorten the course of treatment, improve the safety of treatment, and help the patients recover rapidly.