Background: Pancreatic cancer is a common malignant tumor of digestive system. It has the characteristics of low early detection rate, large surgical trauma and high mortality. Multiple studies have shown that the PLOD family genes are closely associated with tumor progression and metastasis in many human cancers. However, The prognosis and biological function of PLOD family genes in PAAD have not been deeply discussed.Methods: GEPIA,GEO,HPA,CCLE,Kaplan-Meier Plotter,cBioPortal, LinkedOmics, DAVID6.8, STRING and TIMER were used to determine the prognostic values and biological function of PLOD family members in pancreatic cancer.Results: The mRNA and protein expression patterns of PLOD family members were noticeably upregulated in PAAD compared to normal tissue. In addition, PLOD family gene expression is also upregulated in pancreatic cancer cell lines.PLOD1 was significantly correlated with histological grade and pathological grade of pancreatic cancer. PLOD2 is related to histological grade.The high expression of PLOD1-2 was significantly correlated with the poor overall survival rate and relapse-free survival rate in patients with PAAD. In addition, PLODs has high sensitivity and specificity in distinguishing pancreatic cancer from normal tissues.Through the functional enrichment analysis of PLODs-related genes in pancreatic cancer, we found that PLODs was enriched in collagen fiber tissue structure, lysine degradation and collagen biosynthesis.Pathway analysis was confirmed PLODs regulates the proliferation, migration, and metastasis of pancreatic cancer through the RalGEF-Ral signaling pathway.The expression levels of PLOD1–2 were positively correlated with the activities of tumor-infiltrating immune cells, including CD8+T cells, neutrophils, macrophages and dendritic cells.The expression level of PLOD3 was inversely correlated with the infiltration level of CD8+T cells.The expression levels of PLOD1 were higher in pancreatic cancers with TP53 mutations as compared to pancreatic cancers without mutations.PLOD2 expression levels were increased in KRAS mutant pancreatic cancer.However, the expression level of PLOD3 is elevated in SMAD4 wild-type pancreatic cancer.Conclusion: The findings of this study could propose that individual PLOD genes or PLOD family genes as a whole could be potential prognostic biomarkers for PAAD.