We hypothesize that EGF may act as an initiator factor, also called ‘first-hit factor’, to induce the occurrence of HCC inflammatory microenvironment and increase HCC metastasis, and then HCC-origin inflammatory cytokines (e.g. CXCL5 and CXCL8) may act as the second hit to metastasis and development of HCC (Fig. 10). This evidence concerns the gene EGF and hepatocellular carcinoma.