AbstractSilk fibroin is a very promising biomedical material because of its renewability, nontoxicity, biocompatibility, and biodegradability. On the basis of a simple and mild method for the preparation of silk fibroin nanospheres with controllable size, the authors developed earlier, anti‐cancer drug paclitaxel (PTX)‐loaded silk fibroin nanospheres ranging from 270 to 520 nm were produced accordingly. The drug loading, encapsulation efficiency, and released property of PTX‐loaded silk fibroin nanospheres are depended on the silk fibroin concentration and initial PTX‐loading capacity. The maximum drug loading is about 6.9% and the release time of such a kind of nanospheres is over 9 days. The release time of PTX‐loaded silk fibroin nanospheres can be as long as 2 weeks when the drug loading is about 3.0%. All these results imply that such a kind of biomacromolecule‐based anti‐cancer drug nanocarrier has a great potential for chemotherapy in clinical applications. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.