Curcumin has been shown to exhibit anti-neoplastic effects. However, due to its poor bioavailability, use of curcumin as an anti-cancer drug is limited. It is thus necessary to identify molecules that could be targeted using anti-cancer agents as alternatives to curcumin. For this, it is important to understand the underlying signaling pathways mediating the anti-neoplastic effects of curcumin. We carried out phosphoproteomic analysis (TiO2-based enrichment of Ser/Thr kinases) of head and neck cancer cell line, CAL27 treated with curcumin to identify curcumin mediated signaling pathways. This resulted in the identification of 5921 phosphopeptides (phosphosite probability≥75%) corresponding 1,878 proteins. Of these, 275 and 335 phosphopeptides corresponding to 183 and 242 proteins (≥2.0-fold) were found to be hyper- and hypo-phosphorylated respectively, in response to curcumin treatment