Silk fibroin-poly(lactic-co-glycolic acid) fibrous membranes were electrospun by varying the weight ratios for silk fibroin to poly(lactic-co-glycolic acid). The hydrophilicity, mechanical property, and biodegradability of the fibrous in vitro were evaluated. Contact angle test demonstrated that the hydrophilicity of poly(lactic-co-glycolic acid) fibrous membrane could be improved by introducing silk fibroin ingredient. Mechanical test showed that the strain-elongation performances of silk fibroin-poly(lactic-co-glycolic acid) fibrous can be controlled by changing the silk fibroin percentage. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay test showed that the silk fibroin-poly(lactic-co-glycolic acid) 2:8 fibrous enhanced the nerve cell proliferation compared to poly(lactic-co-glycolic acid) fibrous. Silk fibroin-poly(lactic-co-glycolic acid) fibrous membrane has been made into the nerve guidance conduit by the reeling and the sewing processing. The poly(lactic-co-glycolic acid) nerve guidance conduit and silk fibroin-poly(lactic-co-glycolic acid) nerve guidance conduit were implanted into a 10-mm sciatic nerve defect part of mice for nerve regeneration and the nerve regenerated at 12weeks. Nerve regeneration test showed that the regenerated nerve in the silk fibroin-poly(lactic-co-glycolic acid) nerve guidance conduit group was more organized and mature than that in the poly(lactic-co-glycolic acid) nerve guidance conduit group. The results suggest that the silk fibroin-poly(lactic-co-glycolic acid) (2:8) nerve guidance conduits have potential applications in nerve regeneration.