The long noncoding RNA DUXAP8 has been implicated in the progression of various malignancies, including hepatocellular carcinoma (HCC). Although there is increasing evidence of DUXAP8's role in tumor biology, the exact mechanisms by which it affects the development and treatment of HCC are still unclear. Previous studies have suggested a potential link between DUXAP8 expression and disease progression, necessitating further investigation into its roles and underlying mechanisms. To clarify how DUXAP8 is involved in HCC, we measured its expression in HCC cell lines and tissues from patients. We utilized in vitro assays to evaluate the effects of DUXAP8 on tumor cell proliferation and metastasis. Additionally, we examined the regulatory relationships between DUXAP8, YY1, and DEPDC1 using RNA immunoprecipitation and luciferase reporter assays to investigate their functional mechanisms. Our findings demonstrated that DUXAP8 is frequently upregulated in HCC specimens and that its overexpression significantly enhances both the proliferation and metastatic capability of HCC cells. Importantly, the expression levels of DUXAP8, YY1, and DEPDC1 showed correlations with clinical parameters such as disease stage and histopathological characteristics. Mechanistically, we uncovered that YY1 regulates DUXAP8, which, in turn, modulates DEPDC1 expression through a dual mechanism involving the sponging of miR-7-5p and the stabilization of DEPDC1 mRNA facilitated by HNRNPF. Our study identifies DUXAP8 as a pivotal factor in the proliferation and metastasis of HCC, acting through the DUXAP8/miR-7-5p and DUXAP8/HNRNPF pathways to regulate DEPDC1 expression. These findings indicate that targeting DUXAP8 could be a new therapeutic strategy for treating HCC. Further research in both preclinical and clinical settings is needed to evaluate its potential as a biomarker and therapeutic target in liver cancer management.