A series of the Guiqi polysaccharides/chitosan/alginate composite hydrogel microspheres (GPcM) with different particle sizes were prepared with Guiqi polysaccharides (GP), chitosan (CS) and sodium alginate (Alg). The optimum preparation process was also determined by single factor and orthogonal experiment analysis. The GPcM were characterized by fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), drug loading efficiency test (LE), encapsulation efficiency test (EE) and in vitro release study. The results showed that the Guiqi polysaccharides chitosan hydrogel (GPCH) and sodium alginate hydrogel (SAH) formed a crossover system in GPcM. The GPcM have a uniform particle size ranging from 395.1 mu m to 841.5 mu m. The drug loading efficiency and encapsulation efficiency of the GPcM were 56.3% and 72.6%, respectively. The bovine serum albumin (BSA) loaded in the GPcM released slowly within 180 h. The results suggested that the GPcM may have potential application value in drug sustained and controlled release system.