Hepatocellular carcinoma (HCC) has high morbidity and mortality rates, and the number of new cases and deaths from liver cancer are increasing. However, the details of the regulation in HCC remain largely unknown. Plant homeodomain finger protein 8 (PHF8) is a JmjC domain-containing protein. Recently, PHF8 was reported to participate in several types of cancer. However, the biological function and clinical significance of PHF8 in HCC remain unknown. In this study, we investigate the role of PHF8 in HCC growth and metastasis. We used bioinformatics analysis and identified the differentially expressed PHF8 in primary HCC and metastasis HCC. Immunohistochemistry analysis demonstrated that PHF8 was expressed higher in human HCC tissues than in corresponding adjacent noncancerous tissues. Silencing PHF8 in HCC cells significantly decreased the cells' ability of proliferation, migration, invasion, and sphere formation. On the contrary, overexpression of PHF8 promoted these properties. In addition, the analysis in vivo showed that PHF8 overexpression promoted tumor formation and metastasis in nude mice. In the end, the RNA-sequence assay showed that CUL4A is upregulated by the PHF8. Taken together, these results demonstrated that PHF8 was a novel oncogene in HCC, which may contribute to therapeutic approaches aimed at targeting components of the PHF8 and provide new insights into the mechanisms governing the developmental programs in HCC.