Background Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide, largely due to late diagnosis, high rates of tumor recurrence, and resistance to conventional chemotherapy. Despite advancements in surgical techniques and chemotherapeutic regimens, the prognosis for HCC patients remains poor. Consequently, there is an urgent need for novel therapeutic strategies. The identification of molecular targets has revolutionized treatment in various malignancies, such as lung cancer, highlighting the necessity for similar approaches in HCC. Paternally expressed gene 10 (PEG10), an imprinted gene located on chromosome 7, has been found to be overexpressed in a variety of human cancers, particularly those affecting the gastrointestinal tract. This study aims to investigate the expression of PEG10 in HCC and evaluate its potential as a prognostic biomarker. Methods To assess the expression levels of PEG10, mRNA was quantified in human normal liver cell lines and HCC cell lines using quantitative reverse transcription polymerase chain reaction (qRT-PCR). A recombinant plasmid containing PEG10 was utilized in a tumorigenicity assay in a nude mice model to evaluate the in vivo tumor-promoting effects of PEG10. Furthermore, PEG10 mRNA levels were analyzed in a human HCC cDNA array, which included samples from patients with various stages of HCC, inflammatory liver diseases/ non-tumor tissues. Results Our findings indicate that PEG10 expression is weak in normal liver cells but significantly elevated in HCC cell lines. In vivo experiments demonstrated that PEG10 enhances tumorigenicity compared to control groups, suggesting its role in promoting tumor growth. Additionally, analysis of the human HCC cDNA array revealed significant differences in PEG10 mRNA levels between early-stage and late-stage HCC, inflammatory liver disease and HCC, and non-tumor and tumor tissues. Conclusion PEG10 plays a critical role in the pathogenesis of hepatocellular carcinoma, with augmented expression specifically in HCC and not in benign liver conditions. This differential expression suggests that PEG10 may serve as a valuable diagnostic marker, particularly for well-differentiated HCC. Furthermore, the tumorigenic properties of PEG10 highlight its potential as a molecular target for future therapeutic interventions in HCC. Continued research into the mechanisms regulating PEG10 expression and function could pave the way for novel, targeted treatment strategies, ultimately improving outcomes for patients with HCC.