OBJECTIVE：  To observe therapeutic efficacy and safety of Sodium hyaluronate eye drops combined with 0.1％ Fluorometholone eye drops in the treatment of moderate and severe dry eye syndrome. METHODS： 96 patients （198 eyes） diagnosed as moderate and severe dry eye syndrome were randomly divided into observation group and control group with 48 cases in each group （96 eyes）. Control group received Sodium hyaluronate eye drops 0.04 ml， tid； observation group was additionally given 0.1％ Fluorometholone eye drops 0.04 ml， tid， on the basis of control group. Both groups received 4 weeks of treatment. Eye symptom score， cornea fluorescent staining， tear film breakup time， lacrimal secretion， clinical efficacy and ADR were observed in 2 groups before and after treatment. RESULTS： After 2 and 4 weeks of treatment， eye symptom score， cornea fluorescent staining and tear film breakup time of observation group were improved significantly， and better than control group， with statistical significance （P＜0.05）. There was no statistical significance in lacrimal secretion between 2 groups before and after treatment （P＞0.05）. After treatment， total effective rate of observation group （97.92％） was significantly higher than that of control group （86.46％）， with statistical significance （P＜0.05）. There was no statistical significance in the incidence of ADR between 2 groups （P＞0.05）. CONCLUSIONS： Sodium hyaluronate eye drops combined with 0.1％ Fluorometholone eye drops  can improve therapeutic efficacy of moderate and severe dry eye syndrome， with good therapeutic efficacy.