<i>Corn silk</i> contain inherently substantial flavonoid that contribute to its antioxidant and anticancer activity. The objective of the present study was to fabricate a system for efficient delivery of the anticancer compounds using microencapsulation technique. Methanolic corn silk extract was microencapsulated in the polymer Poly (d,l-lactide-co-glycolide) – PLGA using the solvent extraction method. The physicochemical properties such as size, morphology and physical state of free and encapsulated microparticles were measured by dynamic light scattering, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The <i>in vitro</i> release of compounds were studied and quantified using High Performance Liquid Chromatography (HPLC). Spherical and relatively small (d=485.9) polymeric microparticles were obtained containing flavonoids with encapsulation efficiency (EE) of 60.66%. <i>In vitro</i> release profile exhibit a slow, sustained release and follows the first order kinetic with release rate 3.34 x 10<sup>-3</sup> m<sup>-1</sup>s<sup>-1</sup>. The release characteristics data showed that the drug is released from the microsphere even after 108 h. For <i>in vitro</i> cell-based assays, the MTT cell viability assay was performed on HeLa, NIH 3T3 cell lines while cellular uptake of the drug was studied using fluorescence microscopy. Fluorescence studies confirm drug uptake by the cells within 24 h of treatment. For confirmation of mode of cell death Flow Cytometry and DNA ladder assay was performed. The blank polymeric microparticles were non-toxic to cell while, the drug loaded microparticles exhibit apoptic cell death. Thus an efficient delivery system is achieved after encapsulation, that provides protection and controlled release of the bioactive compounds.