Abstract Background: Prostate cancer (PCa) is a common malignant tumor in males, and castration-resistant prostate cancer (CRPC) represents an advanced stage with limited treatment options and poor prognosis. Talin-1 (TLN1) is a cytoskeletal protein implicated in tumor progression, but its specific role and mechanism in CRPC remain unclear. Methods: Mass spectrometry (MS) was used to analyze serum peptides from patients with hormone-sensitive prostate cancer (HSPC) and CRPC.