Reversible addition-fragmentation chain transfer (RAFT) polymerization is a facile means for the controlled synthesis of various functional polymers with predeterminedmolecular weights, narrow molecular-weight distributions, and controlled architectures. Many synthetic polymers are smart carrier candidates for their potent application in medicine, especially in controlled drug delivery. These materials can be loaded with specific drugs for therapeutic applications, releasing treatment in response to a stimulus. In this era of new technologies, there is an ongoing interest in enhancing the efficiency of polymer-based drug delivery systems, in particular crosslinked hydrogel systems [1]. In this work, novel modified nanohydrogel carrier is introduced as efficient host for methotrexate conjugation using 2-hydroxyethyl methylacrylate (HEMA) based RAFTpolymerization. The chemical structure and the topography characterization were carried out by FT-IR, 1HNMR, DLS, SEM, TEM, and AFM. To illustrate the efficiency of the modified particles, the anti-cancer drug methotrexate was conjugated to hydroxyl groups through estric bond formation. The controlled release activity of established nanoparticles was evaluated in simulated cellular fluid. Later, the anticancer behavior of drug conjugated nanoparticles was evaluated in vitro in MCF-7 cell line which showed enhanced toxicity after 48 h. 1H-NMR spectroscopy showed detailed information about poly (HEMA-co-PEG) and made the facility of the molecular weight’s determination. DLS studies of the diluted HEMA-PEG dispersions confirmed successful particle formation. The gel permeation chromatography (GPC) profiles of the poly (HEMA-co-PEG) show Molecular weight and molecular weight distribution. It is very obvious that the molecular weights increase with the increasing conversions in the experimental condition, suggesting the propagation of living chain with time. Conclusively, the modified nanoparticles have remarked as powerful carrier to be applied as an anti-cancer agent.