【Abstract】 Objective The clinical efficacy of hydroxychloroquine sulfate combined with total glucosides of paeony and ilammod in the treatment of primary Sjogren's syndrome was analyzed. Methods The random number table of 76 pSS patients admitted to the outpatient department of rheumatology and immunology in the hospital from February 2018 to February 2019 was divided into two groups, each with 38 patients. The control group was treated with hydroxychloroquine sulfate 200 mg/time, 2 times/d, the total glucosides of paeony capsules 600 mg/time, and 3 times/d orally. The observation group was combined with ilamold tablets 25 mg/Oral treatment twice, twice daily. The treatment indexes were compared after 24 weeks of treatment in the two groups to evaluate the clinical efficacy and safety of different treatment regimens. Results The number of serum immunoglobulin, erythrocyte sedimentation rate, Creactive protein and CD19+CD5+B lymphocytes in the two groups decreased significantly after 24 weeks of treatment compared with that before treatment. After treatment, the laboratory indexes of the observation group decreased better than that of the control group. After treatment, the eye Schirmer test and salivary gland flow rate in the observation group were significantly higher than the control group, and the number of joint swelling and VAS score were significantly lower than the control group, with statistically significant differences (P＜0.05). After 24 weeks of treatment, the total clinical efficiency of the observation group was 8684% significantly higher than that of the control group (57.89%), with statistically significant difference (P＜0.05). The incidence of adverse reactions such as nausea, vomiting and diarrhea in the observation group was 18.42%, slightly higher than that in the control group (13.16%), but the comparison between the groups was not statistically significant (P＞0.05), and no significant abnormalities in routine hematuria and liver and kidney function indexes were observed in the two groups during treatment. Conclusion Primary Sjogren's Syndrome is based on conventional hydroxychloroquine sulfate combined with total glucosides of paeony, and the reasonable combination of a new drug independently developed by our country, Elamod, can further improve the clinical efficacy and accelerate the improvement of patients' symptoms without serious adverse reactions. The new medication plan has higher application value.