Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. PHD finger protein 19 (PHF19) encodes a member of the polycomb group (PcG) of proteins that functions by maintaining the repressive transcriptional states of many developmental regulatory genes. In addition, it has been shown that miR-195 plays an important role in the molecular etiology of HCC; however, the effect and possible mechanism of PHF19 on HCC is unclear, and the association between PHF19 and miR-195 has seldom been addressed. In the present study, we investigated the carcinogenic activity and mechanism of PHF19 on HCC in vivo and in vitro. Our results showed that PHF19 is a potential target of hsa-miR-195-5p based on a bioinformatic analysis and results of a luciferase reporter assay. PHF19 was downregulated after transfection with hsa-miR-195-5p mimics. Moreover, we demonstrated that overexpression of PHF19 promoted hepatoma cell migration, invasion and proliferation in vitro. In contrast, overexpression of hsa-miR-195-5p in hepatoma cells reduced PHF19 expression, leading to suppression of hepatoma cell invasion, migration and proliferation in vitro. In addition, PHF19 markedly promoted the growth of xenograft tumors, while hsa-miR-195-5p markedly suppressed the growth of xenograft tumors in nude mice. These results provide evidence that PHF19 promotes HCC and is regulated by the tumor-suppressor, miR-195-5p.