Objective The study aims to observe the occurrence and risk factors of postoperative depression in patients undergoing non‑cardiac surgery. Methods A retrospective analysis was conducted according to the medical records of 394 patients with non‑cardiac surgery admitted to Affiliated Beijing Chaoyang Hospital of Capital Medical University from September 2019 to December 2019. According to the occurrence of postoperative depression, the patients were divided into the depression group (n=65) and the non‑depression group (n=329). The clinical data of the two groups were compared, and multiple Logistic regression was used to analyze the risk factors of depression after non‑cardiac surgery. Results Out of 394 patients, 65 (16.50%) patients developed postoperative depression. The ratio of preoperative depression, preoperative anxiety, preoperative insomnia, postoperative analgesia, postoperative nausea, postoperative vomiting, the proportion of chest and spine in the surgical site and postoperative Visual Analogue Scale (VAS) score in the depression group were higher than those in the non‑depression group (P<0.05); while the operation time, the ratio of smoking and the proportion of head, face, neck, abdomen, pelvis, upper limbs, and lower limbs in the surgical site were lower than those in the non‑depressed group (P<0.05). Multiple Logistic regression analysis showed that preoperative anxiety [odds ratio (OR)=3.566, 95% confidence interval (CI) 1.754‒7.250, P<0.001] and postoperative pain (OR=1.330, 95%CI 1.158‒1.528, P<0.001) were independent risk factors for depression in patients undergoing non‑cardiac surgery. Conclusions Preoperative anxiety and postoperative pain were independent risk factors for postoperative depression in patients undergoing non‑cardiac surgery. Therefore, the alleviation of perioperative anxiety and pain plays a positive role in reducing the occurrence of postoperative depression.