Salecan is a novel water-soluble β-glucan produced by a salt-tolerant strain Agrobacterium sp. ZX09 which was isolated from a soil sample in our laboratory and the 16S rDNA sequence of this novel strain was deposited in the GenBank database under the accession number GU810841. Salecan has excellent physicochemical properties and can be used in industries such as food and medicine. In this paper, novel semi-interpenetrating polymer network (semi-IPN) hydrogels based on salecan and polyacrylamide (PAAm) were synthesized by radical polymerization/cryopolymerization and semi-IPN techniques. The resulting hydrogels with different salecan/PAAm composition ratios and preparation temperatures were characterized using FTIR, XRD, TGA and SEM measurements. The semi-IPNs exhibited a homogeneous porous architecture with a tunable pore size in a very broad range of 5–150 μm. Furthermore, swelling behaviors of the hydrogels were also studied to investigate the response properties of the hydrogels. The hydrogels obtained at subzero temperature can attain the equilibrium state in water within 260 seconds. Mechanical measurements showed that all semi-IPNs possessed good mechanical properties. In vitro degradation was also studied in PBS solution. Cytotoxicity results suggested that semi-IPN hydrogels were non-toxic to COS-7 cells. A cell culture experiment performed using COS-7 cells revealed their appropriateness for cell adhesion. Together, these results make salecan/PAAm semi-IPNs promising materials for biomedical applications.