Objective To evaluate the feasibility and safety of opioid-free anesthesia in non-intubated thoracoscopy surgery.Methods Sixty patients undergoing thoracoscopic, aged 50 to 70 years, with body mass index of 20 to 24 kg/m2, of American Society of Anesthesiologists physical status (ASA) I or II, scheduled for thoracoscopy surgery under general anesthesia, were randomly divided into either opioid-free anesthesia group or control group with a random number table, 30 patients in each group. In opioid-free anesthesia group, laryngeal mask was placed after opioid-free anesthesia vein induction and muscle relaxant was not used during the operation. In control group, conventional double-lumen endobronchial catheters were used to achieve single-lung ventilation during surgery. Side effects, such as intraoperative choke to cough, hypoxemia, carbon dioxide accumulation, hypertension, hypotension, tachycardia, bradycardia, were recorded. The anesthesia satisfaction score, operative field exposure score, operation time, recovery time, extubation time, post-operation activity time after operation, and postoperative hospital stay were recorded. Adverse reactions with 24 h were recorded.Results There was no statistically significant difference between the two groups in terms of anesthetic effect and degree of satisfaction with surgical field exposure (P > 0.05). However, there was a statistically significant difference between the two groups in terms of postoperative recovery time, extubation time, post-operation activity time, and discharge time (P < 0.05). There was no significant difference in the incidence of cough, hypoxemia, and carbon dioxide accumulation between the two groups (P > 0.05). There were 7 cases of adverse events in opioid-free anesthesia group and 21 cases in control group, comparison between groups was statistically significant difference (P < 0.05). Postoperative respiratory depression, agitation, itchy skin, and dizziness appeared in opioid-free anesthesia group was obviously less than the control group, the difference was statistically significant (P <0.05). There was no statistically significant difference in postoperative nausea and vomiting within 24 h (P > 0.05). However, in the early postoperative period, the incidence of nausea and vomiting in the opioid-free anesthesia group was significantly lower than that in the control group (P < 0.05).Conclusion Opioid-free anesthesia in non-intubated thoracoscopy surgery is safety and effective and reduces adverse effect, which is beneficial to the patient early postoperative recovery.