A novel pH-sensitive and macroporous NaAlg-based hydrogels were prepared, the monomers of which were N -methylolacrylamide (NMAAm) and acrylic acid, using N , N -methylene-bis-acrylamide (MBA) as a cross-linker, 2,2-dimethoxy-2-phenylacetophenone as a photoinitiator via ultraviolet irradiation. The morphology, thermal property and structure of hydrogel were characterized by Fourier transform infrared spectroscopy, scanning electron microscope, X-ray diffractometer and thermogravimetric analysis. The swelling ratios (SRs) of hydrogel were investigated in water, salt and pH solutions. The SR of hydrogel in water increased from 8.1 to 19.4 g/g with increase in weight of NaAlg from 0.2 to 1.0. The result indicated that hydrogel displayed favorable pH- and salt-sensitive. 5-fluorouracil (5-FU) as a model drug was loaded on hydrogel, the drug encapsulation efficiency of products reached to 85.2%, and the cumulative release rate of drug was 78.4 and 37% in the intestinal and gastric fluid, respectively. In addition, the dynamic data of drug release were evaluated by different mathematical models, and the experimental results revealed that it was more fitted to Ritger–Peppas and Higuchi equation models, correlation coefficients ( R 2 ) of which were up to 0.99.