Background <p>Postoperative delirium (POD) in elderly hip fracture patients has a poor prognosis, and the effect and mechanism of dexmedetomidine (Dex) combined with pericapsular nerve group (PENG) block on POD are unclear. To explore the improvement effect of Dex combined with PENG block on POD in elderly hip fracture patients and the regulatory role of miR-107.</p> Methods <p>Eighty-four elderly hip fracture patients (July 2022–December 2023) were divided into PENG block group (<i>n</i> = 28), Dex group (<i>n</i> = 27), and combined group (<i>n</i> = 29). NRS, MMSE, and POD incidence (CAM) were evaluated at T0 (preoperative), T1 (postoperative day 1), and T2 (postoperative day 7); serum miR-107 expression was detected and correlated. A mouse POD model and LPS-induced SH-SY5Y cell model were established; Morris water maze, Y-maze, open field test, ROC, logistic, CCK-8, ELISA, qPCR, and dual-luciferase assay were used for mechanism verification.</p> Results <p>No significant differences were found among the three groups at T0. At T1 and T2, the combined group had lower NRS scores, higher MMSE scores, lower POD incidence (<i>P</i> &lt; 0.05), and upregulated serum miR-107 (<i>P</i> &lt; 0.001). miR-107 was positively correlated with MMSE (<i>P</i> &lt; 0.001) and negatively correlated with NRS (<i>P</i> &lt; 0.05). Animal/cell experiments showed Dex upregulated miR-107, inhibited FBXW7 and inflammatory factors, and improved cognition; miR-107 directly targeted FBXW7.</p> Conclusions <p>Dex combined with PENG block alleviates POD in elderly hip fracture patients by upregulating miR-107 to inhibit FBXW7 and neuroinflammation.</p>