Objective To investigate the effect of perioperative application of a subanesthetic dose of esketamine on acute pain and early recovery quality of patients undergoing thoracoscopic lung surgery. Methods A total of 80 patients who were scheduled for thoracoscopic lung surgery were selected. According to the random number table method, they were divided into two groups (n=40): an esketamine group (group K) and a control group (group C). On the basis of standardized general anesthesia program, group K was intravenously injected with esketamine at 0.2 mg/kg after anesthesia induction, followed by continuous intravenous pumping at 0.1 mg·kg−1·h−1 until the end of surgery, while patient-controlled intravenous analgesia (PCIA, sufentanil 0.03 μg·kg−1·h−1+esketamine 0.015 mg·kg−1·h−1) was given after surgery. Group C was infused with an equal volume of normal saline at the same rate, followed by postoperative PCIA (sufentanil at 0.03 μg·kg−1·h−1). Then, their operation time, anesthesia time, the intraoperative dosages of propofol and remifentanil, and extubation time were recorded. Both groups were compared for the Numerical Rating Scales (NRS) scores at rest and during coughing at postoperative 4, 12, 24 h and 48 h. The scores of 40-items Quality of Recovery Scale (QoR-40) were recorded one day before surgery, and at postoperative 24 h and 48 h. The consumption of sufentanil within postoperative 0‒4 h, 4‒12 h, 12‒24 h, 24‒48 h and 48 h and adverse reactions within 48 h after surgery were recorded. Results Compared with group C, group K showed decreased NRS scores at coughing at postoperative 12 h (P<0.05), increased QoR-40 scores at postoperative 24‒48 h (P<0.05), and decreased consumption of sufentanil within postoperative 48 h (P<0.05), without statistical differences in other indexes (P>0.05). There was no statistical difference in adverse reaction incidence within postoperative 48 h between the two groups (P>0.05). Conclusions Perioperative application of a subanesthetic dose of esketamine in patients undergoing thoracoscopic lung surgery can alleviate acute pain after surgery, reduce the usage of opioids and promote early recovery quality.