A combination of sorafenib and niclosamide can yield a synergistic combination index (CI) for sorafenib-resistant HCC cells that decrease the expressions of IGF-1R/p-IGF-1R/OCT4, attenuate stemness-related properties, downregulate the glycolysis-associated gene expressions, and reduce the mitochondrial membrane potential in vitro, and decrease tumor size and tumor volume resulting from apoptosis in vivo. Here, POU5F1 is linked to hepatocellular carcinoma.