AIM: To observe the effect of Esketamine combined with sufentanil on analgesia and emotion after thoracoscopic radical resection of lung cancer. METHODS: A total of 108 patients undergoing thoracoscopic radical resection of lung cancer were randomly divided into three groups: Esketamine plus sufentanil patient-controlled analgesia group (S group), low-dose sufentanil patient-controlled analgesia group (LC group) and high-dose sufentanil patient-controlled analgesia group (HC group). PCIA was performed after operation. The formula of analgesia pump in group S: Esketamine 1.2 mg/kg, sufentanil 1 μg/kg, LC group analgesic pump formula: sufentanil 1 μg/kg; Formula of analgesic pump in HC group: sufentanil 1.5 μg/kg; Tropisetron 10 mg was added to three groups of analgesia pumps, and normal saline was diluted to 100 mL. Observe the visual analogue scale (VAS) and Ramsay sedation score of resting and exercise pain at 6 h (T1), 12 h (T2), 24 h (T3) and 48 h (T4) after surgery in both groups, evaluate and record the scores of SAS and SDS at 24 h (T0) before surgery, 24 h (T3), 48 h (T4), 72 h (T5) after surgery, and 7 d (T6) after surgery. Record the times of rescue analgesia, the times of effective pressing of the analgesia pump within 48 hours after operation, the times of ineffective pressing, and the occurrence of adverse reactions. RESULTS: In terms of anxiety, there was no difference in SAS scores among the three groups of T0. The SAS scores of T3 and T4 in S group and HC group were lower than those in LC group (all P<0.05). The SAS scores of T5 and T6 in the three groups were not statistically significant (all P>0.05); In terms of depression, the number of patients with depression in T0 group was not statistically significant (P>0.05), the number of patients with depression in T3, T4, T5 in AS group was less than that in LC group and HC group (P<0.05), and the number of patients with depression in T6 group was not statistically significant (P>0.05); In terms of analgesia, the VAS scores of rest and exercise in T1 group were not statistically significant (all P>0.05). The VAS scores of T2, T3, T4 in S group and HC group were lower than those in LC group (all P<0.05). The times of PCIA self-control and ineffective pressing in LC group within 48 hours after surgery were higher than those in S group and HC group (P<0.05). There was no significant difference in the times of pain relief in the three groups after surgery; In terms of adverse reactions, nausea, vomiting and skin itching in group S and LC were better than those in group HC (all P<0.05). There was no statistical significance in terms of sleepiness, respiratory depression, separation symptoms and nightmares in the three groups. CONCLUSION: Esketamine combined with sufentanil for postoperative analgesia after thoracoscopic radical resection of lung cancer can effectively reduce the scores of depression and anxiety of patients, with good analgesic effect and no increase in the incidence of adverse reactions.