The encapsulation of curcumin using p-sulfonatocalixarene (p-SC4) is an attempt to increase the bioavailability of curcumin by increasing water solubility. The degradation of curcumin due to the basicity of p-SC4 is circumvented by maintaining the pH at 3 using 2% hydrochloric acid. The interaction is studied using UV-visible absorption, emission, transient absorption and excited state lifetime methods. The encapsulation of curcumin with p-SC4 increases the excited lifetime of curcumin, as well as the lifetime of the transients (triplet state of curcumin and phenoxyl radical of curcumin) produced upon irradiation. The mode of interaction is studied using H-1 NMR and ROESY spectral techniques. The stability of curcumin in the presence of p-SC4 and the 2 : 1 ratio of p-SC4 binding with curcumin is established using HR-MS and MALDI-TOF analysis. The amount of enhancement in solubility is studied using the HTLC technique.