Objective To explore the effects of dexmedetomidine (Dex) on postoperative delirium (POD) and peripheral blood inflammatory factors in patients undergoing craniocerebral tumor resection. Methods A total of 80 patients who underwent frontotemporal tumor resection in Beijing Tiantan Hospital Affiliated to Capital Medical University from November 2021 to December 2021 were enrolled. According to the random number table method, they were divided into two groups (n=40): a Dex group (group Dex) and a control group (group control). Among them, 20 cases were excluded for blood samples missing, therefore 60 patients were finally enrolled in this study (30 cases in each group ). Group Dex were intravenously infused with a loading dose of 0.6 μg/kg followed by continuous infusion at 0.4 μg·kg−1·h−1 until intraoperative hemostasis, while the group control were given the same volume of normal saline. Furthermore, other anesthetic agents used in the two group were the same. Then, patients in both groups were evaluated by Richmond Agitation‑Sedation Scale (RASS), the Confusion Assessment Method for Intensive Care Unit (CAM‑ICU), the Three‑Minute Diagnostic Interview for CAM (3D‑CAM) during the initial 5 postoperative days. Their incidences of POD were recorded. The levels of IL‑6 and TNF‑α in blood samples were detected after induction (T1), at the end of infusion (T2) and at the end of operation (T3), as well as in patients with/without POD. Demographic and baseline variables, and intraoperative characteristics were compared between the two groups. The risk factors of POD were screened based on baseline information, perioperative information and previous reports. Those with P<0.1 in the univariate logistic regression analysis were included for multivariate logistic regression analysis, so as to explore the risk factors of POD in neurosurgical tumor patients. Results The proportion of patients using glucocorticoid in the group control was higher than that in the group Dex (P>0.05). There were 6 cases (20%) of POD in the group Dex, which was significantly lower than that in the group control (15 cases, 50%) (P<0.05). There was no significant difference in the levels of IL‑6 and TNF‑α in both groups at each point (P>0.05). For the group control, the levels of IL‑6 at T3 was higher than those at T2 (P<0.05), while the levels of TNF‑α were not significantly different at each time points (P>0.05). For the group Dex, the levels of IL‑6 at T3 were higher than those at T1 and T2 (P<0.05), and the levels of TNF‑α at T3 was higher than that at T1 (P<0.05). No differences were found as to the levels of IL‑6 and TNF‑α in patients with/without POD at each time point (P>0.05). For patients without POD, the levels of IL‑6 at T3 were higher than those at T1 and T2 (P<0.05), and the levels of TNF‑α at T3 were higher than those at T1 (P<0.05). For patients with POD, IL‑6 levels at T3 were higher than those at T2 (P<0.05), but there were no statistical difference in TNF‑α levels at each time points (P>0.05). According to multivariate logistic regression analysis, the protective factor was intraoperative infusion Dex (P=0.014, OR=0.21, 95%CI 0.06, 0.73), and the independent risk factor for POD was age (P=0.023, OR=1.07, 95%CI 1.01, 1.13). Conclusions Continuous intraoperative infusion of Dex can significantly reduce the incidence of postoperative delirium in patients with craniocerebral tumor within the first postoperative five days. It is not observed that Dex prevent the occurrence of POD by reducing inflammatory factors (IL‑6 and TNF‑α).