A novel chitin-based microsphere was developed for anti-cancer drug-delivery purpose in the present study. These biodegradable microspheres were prepared by directly blending chitin with different contents of poly(D,L-lactide-co-glycolide 50:50) (PLGA 50/50) in dimethylacetamide-lithium chloride solution, and following it by coagulating in water via wet phase inversion. Scanning electron microscopy (SEM) micrography of the blend microsphere showed that there are numerous PLGA particulates homogeneously dispersed in chitin matrix, suggesting the occurrence of obvious phase separation from the blended chitin and PLGA 50/50 phase due to their thermodynamic incompatibility. Degradation of the chitin/PLGA 50/50 blend microsphere depends on the surface erosion of chitin phase and bulk hydrolysis of PLGA phase, according to the examinations of SEM and differential scanning calorimetry studies. Weight loss of the chitin/PLGA 50/50 blend microsphere increases with the increase of chitin content in the microsphere. A two-phase drug-release model is observed from the release of chlorambucil from chitin/PLGA 50/50 blend microspheres. The initial stage of drug-release rate increases with the increased chitin content due to the hydration and surface erosion of hydrophilic chitin phase; however, the following stage of slow release is sustained for several days, mainly contributed by the bulk hydrolysis of hydrophobic PLGA phase. In conclusion, such a chitin/PLGA 50/50 blend microsphere is novel and interesting, and may be used as a special drug-delivery system.