Octamer‑binding transcription factor 4 (Oct4) has been identified as a novel transcription factor associated with tumorigenesis, acquisition and maintenance of cancer stem cell characteristics and poor prognosis in tumors. However, the role of Oct4 in tumorigenesis and progression of hepatocellular carcinoma (HCC) has not yet been fully elucidated. In our present study, we observed that the Oct4 expression level was upregulated in HCC specimens as well as in different HCC cell lines. In in vitro experiments, decreased expression of Oct4 by shRNA inhibited the viability and mobility of HCC cells. Furthermore, the loss of Oct4 inhibited HCC cell malignant progression accompanied by downregulated expression of the survivin/signal transducer and activator of transcription 3 (STAT3) pathway. Liver cancer patients with high expression of Oct4 exhibited significantly shorter overall and disease‑free survival. These findings demonstrated that Oct4 plays a vital role in the malignant progression of HCC cells through the survivin/STAT3 signaling pathway, and it may prove to be a novel biomarker associated with patient prognosis and survival.