AbstractFibers made of cellulose (CE) and silk fibroin (SF) are wet spun from solutions in N,N‐dimethylacetamide containing 7% LiCl (w/w). Different coagulation baths (water and ethanol) and spinning conditions are used. By using water as the coagulant, a partial dissolution of SF occurs and negligible variation of the mechanical properties of the CE–SF fibers with respect to the CE fibers is found. Fibers coagulated in ethanol are dimensionally homogeneous and show better properties. A modulus of about 13 GPa and elongation to break of 16% for the blend containing 30% (w/w) SF are obtained with a 20‐mm air gap. The fibers are characterized by FTIR micro‐Raman, scanning electron microscopy, and wide‐ and small‐angle X‐ray analyses. In particular, the X‐ray results show that CE–SF fibers are amorphous with a homogeneous dispersion of small SF domains (1.3 nm) in the CE matrix. These results confirm the good compatibility between the two natural polymers. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 2187–2196, 2007