Silk fibroin (SF) from the Bombyx mori silkworm is an excellent biopolymer due to its biocompatibility and degradation. Self-assembled SF nanoparticles loaded with erlotinib are very promising method to treat breast cancer. The size of SF nanoparticles was about 219 +/- 5.7 nm, the dispersion coefficient was about 0.2 +/- 0.03, the encapsulation efficiency was 7.7%, and the drug loading rate was 1.54%. The characteristics of SF nanoparticles were studied by Fourier transform infrared and transmission electron microscope. The cell experiments confirmed that SF nanoparticles had lower and extended cytotoxicity than that of free drugs. These results showed that self-assembled, biocompatible, and biodegradable SF nanoparticles loaded with erlotinib will have potential prospects in the treatment of breast cancer.