Successful repair of long-distance peripheral nerve injuries remains a challenge in the clinic. Rapid axon growth is a key to accelerate nerve regeneration. Herein, a pure silk fibroin (SF) hydrogel with a combination of high-strength and aligned microgrooved topographic structure is reported. The hydrogels exhibit excellent mechanical properties with high strength. Good biocompatibility also allows the hydrogels to support cell survival. Significantly, the hydrogel with aligned microgrooved structures enables the aligned growth of Schwann cells. Moreover, the hydrogel holds a strong capacity for promoting axon growth and guiding neurite sprouting. Thus, this micropatterned SF hydrogel would have great potential for peripheral nerve regeneration.