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More surgeons had noticed the importance of carbon nanoparticles (CNs) in protection of parathyroid grand in the surgery of thyroidectomy and central lymph lode dissection, but paid less attention to the injection time. The purpose of this study was to investigate whether preoperative injection of CNs can improve the dissection of lymph nodes (LNs) and protect parathyroid grand (PG) for the patients with papillary thyroid carcinoma (TC).A total of 102 consecutive patients were enrolled into this study from August 2016 to June 2017. All the patients were divided randomly into preoperative group and intraoperative group by the injecting time of the CNs. We compared the patients who had CNs injected into thyroid gland 1 month before surgery with a control group of patients who had CNs injected during the operation. The primary endpoints were operative time, numbers of total LN and metastatic LN, ratio of PG auto-transplantation, parathyroid hormone (PTH) level, and postoperative complications.We identify 206 PGs and 162 PGs in the preoperative and intraoperative group, respectively, (P = .000) and there was low ratio of auto-transplantation in the preoperative group compared with the intraoperative group (39.3% vs 50.62%, P = .003). We also found that the PTH level in the preoperative group was higher than that of preoperative group (2.60 ± 1.00 vs 2.19 ± 0.72, P = .021), and the operation time in the preoperative group was less than the intraoperative group (60.17 ± 6.28 vs 80.94 ± 7.12, P = .000). Meanwhile pathological results revealed 3 PGs of accidental removal occurred in the preoperative group, whereas 9 PGs of accidental removal occurred in the intraoperative group (P = .039). Also there was no difference in the numbers of total and metastatic LN in the 2 groups (P > .05).Preoperative injection of CNs was safe, and can help protect PG and reduce the difficulty of operation.