Exosomes, as carriers of cell-to-cell communication, can serve as promising biomarkers for probing the early diagnosis of cancer. Pancreatic cancer is a common malignant tumor of the pancreas with an insidious onset and difficult early diagnosis. The aim of this study was to capture exosomes in urine samples by phosphatidylserine-molecularly imprinted polymers (PS-MIPs). Transmission electron microscopy and nanoparticle tracking analysis as well as Western blot showed that our molecularly imprinted material can effectively capture urinary exosomes. Three parallel tests verified the reproducibility of the mass spectrometry assay and the stability of the material capture efficiency. Mass Spectrometry with nontargeted proteomics was combined to show differentially expressed proteins in exosomes between 5 pancreatic cancer patients and 5 healthy controls. The most significant changes in the proteomic profile in pancreatic cancer patients compared to healthy controls were the overexpression of SLC9A3R1, SPAG9, and ferritin light chain (FTL) These proteins may have an important role in diagnosis and prognostic assessment, supporting further scientific and clinical studies on pancreatic cancer.