Hepatocellular carcinoma (HCC) is one of the most common malignant tumors throughout the world. However, its mortality rate remains very high due to the absence of early diagnostic modalities and effective treatments, and its specific pathogenesis remains unclear. Here, we investigated the role of PNMA1 in the tumorigenesis of HCC. We found that PNMA1 was significantly upregulated in HCC. Clinically, higher expression of PNMA1 was associated with aggressive phenotypes and poor prognosis. Functionally, silencing of PNMA1 repressed proliferation in vitro and in vivo, and knockdown of PNMA1 suppressed tumor cell migration and invasion. Via GSEA analysis, we predicted that PNAM1 may be related to the epithelial-mesenchymal-transition and the Wnt signaling pathway. Both these assumptions were confirmed in our study. Furthermore, we proved that miR-33a-5p participated in the posttranscriptional regulation of PNMA1. Together, our findings suggested that PNMA1 participated in HCC progression and may be a potential biomarker and therapeutic target for HCC.