Purpose <p>Many advanced-stage pancreatic cancers are fatal, highlighting the need for solid prognostic indicators. This study evaluates transferrin receptor-1 (TfR1) expression in pancreatic cancer tissues and cell lines for clinical and therapeutic potential.</p> Method <p>The GuangRe database, which integrates mRNA data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project, was used to assess <i>TFRC</i> gene expression in pancreatic cancer and normal tissues. ROC curves and Kaplan–Meier and Log-rank tests were used to evaluate <i>TFRC</i> gene expression's diagnostic and survival efficacy. In vitro Western blotting and immunofluorescence experiments on pancreatic cancer cell lines assessed TfR1 expression. IHC staining was done on tissue samples from 90 patients to determine TfR1's clinical importance.</p> Results <p>The study found that <i>TFRC</i> mRNA levels were significantly higher in pancreatic cancer tissues compared to nearby normal tissues (<i>P</i> &lt; 0.05), with an AUC of 0.936. We found higher TfR1 protein levels in pancreatic cancer cell lines (<i>P</i> &lt; 0.01) using western blot and immunofluorescence studies. Immunohistochemistry showed that pancreatic cancer tissues expressed 30.1% TfR1 compared to paracancer (11.1%) (<i>P</i> = 0.003). In COX regression analysis, increased TfR1 expression was related with lower overall survival (OS) and progression-free survival (PFS), making it an independent prognostic factor.</p> Conclusion <p>Higher TfR1 expression is associated with poor pancreatic cancer outcomes, suggesting its potential as a prognostic biomarker and therapeutic target.</p>