To investigate the clinical efficacy and safety of the treatment of benign thyroid nodules with Xiaoying Sanjie Decoction combined with levothyroxine. Methods:A total of 125 patients with benign thyroid nodules who were treated in Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University from June 2014 to June 2016 were selected, and the clinical data was analyzed retrospectively. According to different treatments, these patients were divided into study group with 62 cases (levothyroxine solutions combined with Xiaoying Sanjie Fang) and control group with 63 cases (levothyroxine solutions only). After 6 months of treatment, clinical data of curative effect, size of thyroid nodules and adverse toxic reaction of the two groups were compared and T-test and chi square test were applied. Results:The difference of the date of patients before treatment had no significant statistical difference (P?0.05). Compared with prior treatment, the longest diameter, volume and thyroid function of thyroid nodules (TSH) of the two groups were significantly decreased, and it had statistical significance. Compared with control group, overall efficiency of study group was more significant (82.26% vs 50.79%); The changes of longest diameter of thyroid nodules were more significant (4.14±0.67 vs 1.61±0.72 mm); volume reduction was more prominent (2.74±0.91 vs 1.16±0.59 mm); TSH decrease was more appreciable (15.13±4.71 vs 7.97±7.66); The incidence of adverse reaction was lower (11.29% vs 26.98%). Conclusion:Xiaoying Sanjie Decoction combined with levothyroxine solutions for non-surgical benign thyroid nodules is more effective with higher safety than single levothyroxine, and it is worthy for clinical application.