Biocompatible pH-sensitive semi-interpenetration polymeric network hydrogels (semi-IPN) based on water-soluble N-carboxyethyl chitosan (CECS) and 2-hydroxyethyl methacrylate (HEMA) were synthesized by the photopolymerization technique. pH-sensitivity, cytotoxicity, morphology, mechanical property, and water state of hydrogel were investigated by a swelling test, methylthiazolydiphenyl-tetrazolium bromide (MTT) assay, scanning electron microscopy (SEM), universal testing machine, and differential scanning calorimetry (DSC), respectively. The drug release studies were carried out using 5-Flurouracil as the model drug. The results indicated that the hydrogels were sensitive to pH of the medium and its wet state had good mechanical properties. The results of cytotoxicity and prolonged drug release characteristics revealed the suitability of the hydrogels as drug delivery matrices. The release kinetics was evaluated by fitting the experimental data to standard release equations, and the best fit was obtained with the Higuchi model of the hydrogel. Copyright © 2008 John Wiley & Sons, Ltd.