Three synthesized acrylonitrile-graft-silk fibroin copolymers (AN-g-SF), denoted as COP-65, COP-87, and COP-106, were used as potential compatilizers for acrylic polymer-silk, fibroin blend fibers. Due to their different molecular weights and architecture, the compatibilizing efficiency is in the order of COP-106 > COP-65 > COP-87. To maintain the "sheath-core" structure of the blend fiber, COP-65 was chosen as the compatilizer. It was found that the addition of a small amount of COP-65 (up to 2 wt %) results in finer and more even distribution of the SF fibrils. On the contrary, excess COP-65 will cause flocculation and coalescence of the SF phase. Similarly, mechanical properties are enhanced with an optimum amount of the compatilizers. However, when excess COP-65 is added, the mechanical properties of the blend fibers are even worse than that of the uncompatilized samples. The mechanism of these findings is also discussed.