Abstract: Objective To explore the application and effectiveness of fine anatomical dissection of the sternothyroid ligament combined with mitoxantrone injection in papillary thyroid carcinoma surgery. Methods A total of 120 patients who were diagnosed with thyroid papillary cancer by preoperative puncture pathology from January 2020 to December 2022 at Department of Thyroid and Breast Surgery, Lianyungang Second People's Hospital, were selected. According to the random number table method, the patients were divided into three groups: groups A, B, and C. Group A underwent traditional fine capsule dissection surgery, group B received mitoxantrone injection for negative tracing based on group A's approach, and group C received fine anatomical dissection of the sternothyroid ligament on top of group B's method. Their general information, imaging data, and surgical indicators (number of lymph node dissections and surgery duration) were collected. The levels of parathyroid hormone (PTH) and calcium ion (Ca²⁺) before and after surgery were compared. Postoperative pain (visual analog scale, VAS) and complications were also assessed. Results There were no significant differences in general information and tumor invasion among the three groups. Group C had the most lymph node dissections, followed by group B, and group A had the fewest, with significant differences between groups (P<0.017). Surgery duration, intraoperative blood loss, postoperative drainage volume, and drainage tube placement time showed similar trends, and the differences were statistically significant (P<0.017). In terms of the length of hospitalization, group C had a shorter stay than groups A and B, while the surgical and hospitalization costs in group C were higher than in group A (P<0.017), with no significant difference between groups C and B. Pain scores at postoperative 24 h in group C were slightly lower than in groups A and B (P<0.017), but no significant differences were found at postoperative 72 h. On day 1 after surgery, group C showed higher Ca²⁺ and PTH levels than group A. The incidence of complications was highest in group A, followed by group B, and lowest in group C (P=0.033). One serious complication, long-term hypocalcemia, occurred in group A. Conclusions Fine anatomical dissection of the sternothyroid ligament combined with mitoxantrone injection in thyroid cancer radical surgery can effectively identify and preserve the parathyroid glands, increase the number of lymph node dissections, and reduce postoperative complications, with significant clinical application value.