Abstract: Objective To investigate the effects of mecobalamine combined with ropivacaine for intercostal nerve block on the postoperative depression in patients undergoing thoracoscopic surgery. Methods A total of 110 patients who underwent thoracoscopic surgery in the Affiliated Hospital of Xuzhou Medical University were randomly divided into two groups (n=55): a mecobalamine combined with ropivacaine group (an experiment group) and a ropivacaine group (a control group). After surgery, intercostal nerve block was performed. The experiment group was injected with 1 ml of mecobalamin(0.5 mg/1ml) +10 ml of 0.5% ropivacaine+normal saline (totally 20 ml), while the control group was injected with 10 ml of 0.5% ropivacaine + normal saline (totally 20 ml).The Self-Rating Depression Scale (SDS) was used to evaluate the postoperative depression of the two groups.The Numerical Rating Scale (NRS) was used to evaluate the pain of the patients. Results The number of patients with mild pain (NRS score≤ 3) was 40 (78.4%) for the experimental group and was 30 (56.6%) for the control group, which was statistically different (P< 0.05). Two months after surgery,the incidence of depression was 15.7% for the experimental group and 34.0% for the control group, which was statistically different (P<0.05). Conclusions Mecobalamine combined with ropivacaine for intercostal nerve block can reduce the risk of postoperative depression through improving postoperative pain in patients after thoracoscopic surgery.