Background: Hepatocellular carcinoma (HCC) is the second most common cancer-associated cause of death globally. It is thus vital that novel diagnostic and prognostic biomarkers associated with early-stage HCC be identified. While keratin 17 (KRT17) has previously been reported to be associated with certain cancer types, its relationship with HCC remains to be defined. Methods：The expression of KRT17 in the TCGA LIHC database and in 44 pairs of HCC patient samples was assessed via qRT-PCR, western blotting, and immunohistochemical staining. The prognostic relevance of KRT17 was assessed using Kaplan-Meir curves, while important cancer- and KRT17-related biological processes were defined through gene set enrichment analysis (GSEA). The functional link between KRT17 expression and tumor cell proliferation/survival was assessed through flow cytometry, colony formation assay, CCK-8 assay, and subcutaneous tumor model approaches. Protein-protein interaction (PPI) networks and analyses of immune cell infiltration were also employed to define key signaling pathways associated with KRT17 expression in HCC. Results：HCC tissue samples exhibited increased KRT17 mRNA and protein expression that was predictive of poorer patient survival (P<0.001). GSEA and functional experiments revealed that KRT17 functioned as a regulator of HCC tumor cell survival, proliferation, and cell cycle progression in vitro and in vivo. PPI network analyses also revealed that KRT17 expression was linked to immune cell infiltration and activation in patients with HCC. Conclusion: We found that increased KRT17 levels were associated with poorer survival, more aggressive disease, and altered immune cell infiltration in patients suffering from HCC. As such, KRT17 may function as an oncogene and a prognostic biomarker in this cancer type.