As previously reported, triple drugs (docetaxel, cisplatin, and 5−FU) −resistant HNSCC cell lines (Hep−2 and CAL−27) exhibited higher chemotherapy resistance, reduced apoptotic cell death, and an increased expression of MDR1, MRP2, ERCC1, CTR, Survivin, and TS (88), which suggests that multiple drug-resistant HNSCC cells can simultaneously have multidrug cross-resistance mechanisms, including DNA/RNA damage repair, drug efflux, and apoptosis inhibition. This evidence concerns the gene CALCR and head and neck squamous cell carcinoma.