In conclusion, the current study demonstrates that chemokine CXCL1 plays a critical promotive factor via the CXCR2/FAK/PI3K/Akt pathway to upregulate the NF-κB expression and nuclear translocation, and further triggered the NF-κB-dependent VCAM-1 expression enhancing the migration, invasion, and homing abilities of osteosarcoma cells to the lung. The gene discussed is NFKB1; the disease is osteosarcoma.