Abstract: The blend solution prepared by dissolving Silk fibroin (SF) and cellulose acetate (CA) in formic acid at different mass concentrations was electrospun into SF/CA blend fibers and then processed into SF/CA felt. The SF/CA fiber felt was studied by SEM and XRD. The results showed that the spinnability of SF was remarkably improved with a small quantity of CA (no more than 10%), and the blend fibers were fine and uniform with the fiber diameters ranging from 50 nm to 300 nm. When CA content was 10%, the SF/CA blends showed excellent spinnability without any beads or droplets. However, the spinnability of SF/CA deteriorated seriously when the content of CA was more than 30%, and the electrospun SF/CA blend nanofibers were discontinuous, sticky, and forming dendritic structure with lot of beads. The XRD analysis showed that adding a small quantity of CA (no more than 10%) could induce the conformation transition of SF molecules transforming from random coil to β-sheet. Nevertheless, the phase separation was observed between SF and CA in blend nanofibers when the content of CA was more than 30%.