Abstract: Objective To investigate the expression of cyclooxygenase-2(COX-2) and prostaglandin E2(PGE2) in patients with non-functional pituitary adenoma(NFPA) and their relationships with tumor invasion.Methods A total of 82 NFPA patients who underwent transsphenoidal resection of pituitary tumors in the Affiliated Hospital of Xuzhou Medical University and Xuzhou Central Hospital from January 2021 to August 2022 were selected. According to the invasion of pituitary adenomas, the patients were divided into two groups: an invasive NFPA group and a non-invasive NFPA group. Clinical data and biochemical indicators were collected, and the levels of COX-2 and PGE2 in serum and tumor tissue homogenates were detected.Results According to one-factor analysis of variance, the invasive NFPA group showed remarkable increases in the levels of serum COX-2 and PGE2, compared with the non-invasive NFPA group(P＜0.05). Multiple Logistic regression analysis showed that tumor diameter and the levels of serum COX-2 and PGE2 may be the risk factors of invasive NFPA(P＜0.05). The levels of serum COX-2 and PGE2 were positively correlated with the levels of COX-2 and PGE2 in tumor tissue homogenates. The ROC curves showed that the AUC of COX-2, PGE2 and their combination for the diagnosis of invasive NFPA was 0.804, 0.802, and 0.830(P＜0.05). Moreover, clinical variable analyses revealed a significant correlation between the levels of serum COX-2 and PGE2 and tumor diameter, Hardy-Wilson grade and stage, Knosp grade and Ki-67 index in NFPA patients(P＜0.05).Conclusions The levels of serum COX-2 and PGE2 in NFPA patients are closely correlated with invasion. Increases in the levels of serum COX-2 combined with PGE2 may provide effective evidence for assessing the invasive ability of pituitary adenomas.