We have undertaken studies to investigate whether (i) EpoR is expressed in established HNSCC cell lines; (ii) rhEpo promotes cell proliferation and invasion; (iii) rhEpo protects HNSCC cells from cisplatin-induced death, the first-line of chemotherapy treatment for this malignancy; and (iv) the PI3K/Akt signaling pathway is implicated in rhEpo-mediated HNSCC cisplatin resistance. This evidence concerns the gene EPOR and head and neck squamous cell carcinoma.