The results of this study indicate that inhibition of the chemokine receptors, CXCR1/2, can uniquely sensitize cancer cells to the cytotoxic activity of docetaxel, while the combination of CXCR1/2 inhibition plus docetaxel could also reshape the immune microenvironment in HPV-negative HNSCC to promote anti-tumor immunity. Here, CXCR1 is linked to head and neck squamous cell carcinoma.