Our results indicate that CXCR6 antagonism with SBI-457 can modulate β-catenin activation and may improve response to sorafenib in select HCC cells that have high expression of β-catenin, shed soluble CXCL16, and have a high-molecular-weight isoform of CXCR6. The gene discussed is CXCR6; the disease is hepatocellular carcinoma.