CXCR2 is a G-protein-coupled cell surface chemokine receptor, and integrins are heterodimeric transmembrane (TM) glycoproteins. These proteins work together to activate neutrophils in the immune defense, but knowledge of their function in tilapia is limited. RACE technology was used to clone the full length of the Nile tilapia Oreochromis niloticus Cxcr2 gene, which included a 954 bp open reading frame encoding 318 amino acids, and the integrin β2 gene, with a 2373 bp open reading frame and 791 amino acids. Sequence analyses showed that Cxcr2 and integrin β2 are conserved among species. Expression profile was performed using qRT-PCR and indicated that Cxcr2 and integrin β2 were distributed throughout the examined organ tissues, with highest expression observed in the immune tissues. Expression of Cxcr2 and integrin β2 were increased after challenged with Streptococcus agalactiae or Aeromonas hydrophila. Results suggest that Cxcr2 and integrin β2 genes play a role in immune response in Nile tilapia and provide basic data for molecular-assistant selection of disease-resistant bloodstock to improve the production.