The pH-sensitive polymeric materials are the current need of time in targeted drug delivery applications. The pH-sensitive cross-linked psyllium grafted-poly (acrylonitrile-co-acrylic acid) [Psy-g-Poly (An-co-AA)] was synthesized by using ceric ammonium nitrate (CAN) redox initiator via chemical grafting process for colon cancer treatment. The synthesized material [Psy-g-Poly (An-co-AA)] was characterized by nuclear magnetic resonance, Fourier transform infrared, scanning electron microscopy, X-ray diffraction Zeta potential, and thermal gravimetric analysis. Furthermore, quercetin (QPN) drug was encapsulated in cross-linked grafted psyllium preparing nanoparticles of encapsulated QPN via the sonication technique for controlled release of QPN and testing of in vitro anticancer and antioxidant activities. The anticancer activity of QNP and QPN were studied on human cell line (HCT-15) and it was observed that QNP also exhibited excellent anticancer and antioxidant activity as compared to only QPN. QNP showed maximal swelling at pH-7 and demonstrated maximum QPN release (93%) at the pH of the intestinal fluid (pH-7.4). The drug release kinetic data followed the Korsmeyer-Peppas model (R 2 = 0.9808) kinetic model, indicating the mechanism of drug release from QNP was non-Fickian diffusion. Furthermore, pH-specific QPN release behavior of Psy-g-Poly (An-co-AA) can be utilized for colon targeted drug delivery.