This dataset comprises a Tandem Mass Tag (TMT)-based quantitative proteomic analysis of serum samples from patients with postherpetic neuralgia (PHN) compared to healthy control subjects. The study aimed to identify differentially expressed proteins involved in the pathogenesis of neuropathic pain. Peripheral blood serum was collected from three PHN patients and three age- and sex-matched healthy volunteers. Proteins were digested with trypsin, labeled with TMT isobaric tags, and fractionated by reversed-phase liquid chromatography. The peptides were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on a SCIEX TripleTOF 5600+ instrument. Our analysis identified 127 differentially expressed proteins (79 down-regulated and 48 up-regulated in the PHN group). Notably, Endoglin (CD105), a key endothelial cell membrane glycoprotein, was one of the significantly down-regulated proteins. This discovery was subsequently validated by ELISA in a larger cohort (n=30 per group). The proteomic profiling presented in this dataset led to the mechanistic hypothesis that reduced Endoglin expression contributes to neuropathic pain by disrupting the blood-spinal cord barrier (BSCB) integrity via inhibition of the TGF-β/Smad2 signaling pathway. This hypothesis was successfully confirmed in a spared nerve injury (SNI) rat model through behavioral, biochemical, and histological experiments, as detailed in our associated manuscript. This dataset provides the foundational proteomic evidence for the role of Endoglin in neuropathic pain and serves as a valuable resource for identifying potential biomarkers and therapeutic targets.