Novel semi-interpenetrating network (semi-IPN) hydrogels based on biodegradable chitosan and poly(N-isopropylacrylamide-co-2-acrylamido-2-methyl-1-propanesulfonic acid) were prepared by free radical addition polymerization. Fourier transform infrared spectra and scanning electron microscopy were used to characterize the semi-IPN hydrogels and the results showed that chitosan and poly(N-isopropylacrylamide-co-2-acrylamide-2-methyl-1-propanesulfonic acid) semi-IPN hydrogels were coupled by the interaction of the functional groups present in NIPAAm, CS and AMPS units. The PNIPAAm and P(NIPAAm-AMPS)/CS hydrogels have lower critical solution temperature and the same was confirmed with the help of differential scanning calorimetry as well as with the temperature dependent swelling curves. The model anti cancer drug, 5-fluorouracil (5-FU) was loaded into the semi-IPN hydrogels, at ambient temperature. The 5-FU loading capacity and release behaviour were investigated with these hydrogels acting as carriers for controlled release. The released 5-FU concentration was calculated with the help of UV spectrophotometer at 266. 5 nm. © 2012 Springer Science+Business Media, LLC.