Objective: Hyaluronan (HA) is a ligand for the CD44 receptor, which interacts with multiple signaling pathways to influence cellular behavior. We recently determined that HA-CD44 promotes phospholipase C (PLC)-mediated Ca2+ signaling and cisplatin resistance in head and neck squamous cell carcinoma (HNSCC). The objective of this study was to investigate the downstream molecular targets of HA-CD44 and PLC-mediated Ca2+ signaling in HNSCC.