Surgical management is commonly used for thyroid cancer. We evaluated the effects of systemic lidocaine versus dexmedetomidine on the recovery quality and analgesia after thyroid cancer surgery. A total of 120 patients with thyroid cancer were randomly allocated to groupL (received lidocaine 1.5mg/kg loading, continuously infused 1.5mg/kg per hour), groupD (received dexmedetomidine 0.5µg/kg loading, continuously infused 0.5µg/kg per hour) and groupC (received normal saline), with 40 cases in each group. Anaesthesia induction and maintenance were performed using target-controlled infusions (TCIs) of propofol and remifentanil. The primary outcome of the quality of recovery-15 (QoR-15) score was recorded on the day before surgery and postoperative day1 (POD1). Secondary outcomes included the consumption of remifentanil during surgery, time to first required rescue analgesia, number of patients requiring rescue analgesia, postoperative cumulative consumption of tramadol, visual analogue scale (VAS) pain score, incidence of postoperative nausea or vomiting (PONV) and side effects. The total score of the QoR-15 at POD1 (median, IQR) was higher in groupL (128.0, 122.0-132.8) and groupD (127.5, 122.5-132.5) compared to groupC (118.5, 113.0-123.5) (P = 0.000). Compared to groupC, systemic lidocaine and dexmedetomidine reduced cumulative consumption of remifentanil and VAS pain score (P = 0.000). The time to first required rescue analgesia (mean, SD) was longer in groupL (8.1h, 1.2h) and groupD (8.5h, 1.9h) than groupC (5.9h, 0.9h) (P = 0.000). The number of patients requiring rescue analgesia was lower in groupL (8/40, 20%) and groupD (6/40, 15%) than groupC (16/40, 40%) (P = 0.029), and cumulative consumption of tramadol (mean, SD) was lower in groupL (44.0mg, 17.1mg) and groupD (51.7mg, 14.1mg) than groupC (73.9mg, 18.4mg) (P = 0.000). The incidence of PONV in groupL (7/40, 17.5%) and groupD (9/40, 22.5%) was lower than groupC (18/40, 45.0%) (P = 0.016). Bradycardia (heart rate less than 50beats/min or lower) was noted in 25 patients (25/40, 62.5%), which was reversed by intravenous administration of atropine 0.5mg. Systemic lidocaine and dexmedetomidine had similar effects on enhancing the quality of recovery, alleviating the intensity of pain and reducing the incidence of PONV after thyroid cancer surgery. However, dexmedetomidine may result in bradycardia. Therefore, lidocaine was superior to dexmedetomidine. ChiCTR.org.cn (ChiCTR2000038442). Registered on September 22, 2020.