Golgi phosphoprotein 3 (GOLPH3) overexpression has previously been associated with the progression of several solid tumors, which resulted in adverse clinical outcomes. The present study aimed to determine the expression and prognostic significance of GOLPH3 in human hepatocellular carcinoma (HCC). GOLPH3 expression was examined using western blot analysis of 30 paired samples of HCC and adjacent non‑cancerous liver tissues. GOLPH3 expression levels were also assessed using immunohistochemistry in 180 HCC samples and paired controls. In addition, the association of GOLPH3 expression with clinicopathological features and clinical outcome was analyzed. Furthermore, the effect of GOLPH3 on HCC cell proliferation and invasion were determined. Western blot analysis revealed that GOLPH3 expression was significantly elevated in HCC tissue compared with that of the matched adjacent non‑cancerous liver tissue. In addition, the results of the immunohistochemical analysis demonstrated that GOLPH3 expression was positively correlated with the Edmondson‑Steiner grade (P=0.006), vascular invasion (P=0.002) and serum α feto‑protein levels (P=0.015). GOLPH3 expression was found to be an independent factor for predicting the poor overall survival of HCC patients (hazard ratio, 2.01; 95% confidence interval, 1.26‑3.64; P=0.025). In addition, GOLPH3 silencing inhibited the proliferation, invasion and migration of HCC cell lines in vitro. In conclusion, the results of the present study demonstrated that high GOLPH3 levels may be a potential biomarker for the poor prognosis of patients with HCC.