Background and Aims Thyroid mass complicated with hyperthyroidism (TMCWH) is a difficult situation in thyroid surgery. The traditional concept is that patients with primary hyperthyroidism undergoing surgery generally require the use of Lugol's solution for preoperative preparation. However, with the advancement of thyroid surgical techniques and the change of operation methods, this concept has also been questioned and challenged. Therefore, this study was conducted to investigate the clinical effect and safety of performing surgery in TMCWH patients without addition of Lugol's solution in preoperative preparation.Methods The clinical data of 51 consecutive patients with TMCWH admitted from January 2018 to January 2021 were retrospectively analyzed. The general clinical data of the patients, types and doses of anti-thyroid drugs, changes in thyroid function and operation methods as well as the incidence of postoperative complications were summarized.Results There were 36 females and 15 males in the whole group, aged from 30 to 77 years old, with a disease course of 6 months to 22 years and varying degrees of thyrotoxicosis. Forty-nine patients received the combination treatment of methimazole and propranolol for preoperative preparation, of whom, 13 patients were treated with prednisone at the same time; the other two patients only used propranolol and prednisone for preoperative preparation. Two patients underwent thyroid artery embolization before operation. The preoperative preparation time of the whole group was 5-10 d; the preoperative thyroid function of 32 patients did not fully return to normal, but the basal metabolic rate (BMR) of all patients decreased significantly, and maintained at 9% to 15%, and the heart rate was 71 to 85 bpm. Total thyroidectomy was performed in 40 cases, 6 cases underwent unilateral lobectomy plus subtotal or subtotal resection of contralateral lobes, and 5 cases were subjected to unilateral lobectomy. All patients recovered uneventfully after the operation, and no thyroid crisis occurred. In postoperative outpatient follow-up, no hyperthyroidism or tumor recurrence occurred.Conclusion Surgery can be performed in TMCWH patients with T3/FT3 and/or T4/FT4 controlled within 10% of the upper limit, and BMR controlled below 20% after using conventional drugs for preoperative preparation. For TMCWH patients with significantly elevated thyroid-stimulating hormone receptor antibodies, total thyroidectomy or near total resection can be helpful for completely curing the disease.