In the present study, we proved the expression of CCN3 is up-regulated in oxaliplatin-resistant HCC, which induced the remodeling of HSCs with elevation of cytokines such as RANTES, IL-16, IL-1a, IL-13, IL-2, TNFa, TGFβ, and MCP-1 et al., resulting in the maintenance of oxaliplatin-resistance of HCC. The gene discussed is CCN3; the disease is hepatocellular carcinoma.