Background Hepatocellular carcinoma (HCC) is one of the most common malignancies with rising incidence and persistently high mortality. Previous researches have demonstrated that somePLODfamily members are associated with tumor progression and metastasis in most human cancers. However, the prognostic and biological roles ofPLODsin HCC remain largely unknown. Methods ONCOMINE, HPA, UALCAN, GEPIA, cBioPortal, GeneMANIA, NetworkAnalyst, Metascape, DAVID 6.8, and TIMER were used to determine the prognostic values and biological function ofPLODfamily members in HCC. Results The mRNA and protein expression patterns ofPLODfamily members were noticeably upregulated in HCC compared to normal tissue. The high expression levels ofPLOD1andPLOD2genes were significantly correlated with higher tumor grades in HCC patients. In addition, the high expression levels ofPLOD1-3were remarkably associated with poor overall survival in HCC patients, while highPLOD1andPLOD3expression were markedly associated with worse disease-free survival. In the co-expression gene analysis, 20 genes were primarily associated with the differentially expressedPLODfamily members in HCC cases. Through functional enrichment analysis, the biological functions ofPLODsin HCC were mainly involved in collagen fibril organization, lysine degradation, collagen biosynthesis, and modifying enzymes. Furthermore, the expression levels ofPLOD1-3were positively correlated with the activities of tumor-infiltrating immune cells, including macrophages, neutrophils, CD4+ T cells, and dendritic cells. Besides, the expression levels ofPLOD2andPLOD3were positively correlated with the infiltrating levels of B cells. Conclusion The findings of this study could provide novel insights into the identification of prognostic biomarkers for HCC patients.