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Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality globally. Previous studies have reported that oral cancer overexpression 1 (ORAOV1) is overexpressed in HCC and correlated with poor prognosis, yet its molecular mechanisms remain incompletely understood. In this study, ORAOV1 overexpression was confirmed in HCC tissues via tissue microarray analysis and functionally linked to tumor cell proliferation through a positive correlation with Ki-67 expression in the human HCC cell line MHCC-97L. Bioinformatics analyses using The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) HCC datasets further supported these findings. Multiple mechanisms appear to drive ORAOV1 upregulation, including promoter hypomethylation, amplification of the 11q13 region, and a putative ceRNA network involving AC005332.1, AC012615.1, and hsa-miR-100-5p. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses implicated ORAOV1 in various cellular processes, such as abnormal membrane channel function, extracellular matrix-receptor interactions, IL-17 signaling, and peroxisome proliferator-activated receptor (PPAR) signaling. Co-expression analysis identified significant associations between ORAOV1 and the oncogenes TPCN2 and CCND1. Additionally, ORAOV1 expression correlated with enhanced infiltration of immunosuppressive cells, including regulatory T cells, myeloid-derived suppressor cells, and cancer-associated fibroblasts, as well as upregulation of immune checkpoint markers (PD-1, PD-L1, and CTLA-4). These results indicate that ORAOV1 may modulate the immunosuppressive tumor microenvironment and contribute to resistance against immunotherapy, highlighting its potential as a therapeutic target in HCC.