We found that EGF could stimulate CXCL5 production from HCC through the EGF-EGFR-phosphoinositide 3 (PI3K)-kinase-extracellular signal-regulated kinases (ERK) signalling pathway and there was an interaction between CXCL5 and CXCL8 and the cross-talk between chemokine receptor-2 (CXCR2) and EGFR. Here, CXCL5 is linked to hepatocellular carcinoma.