The invention belongs to the technical field of biological cell, and in particular, relates to a method for reprogramming human fibroblasts into mature neurons in high efficiency and large quantity. The method comprises the steps: S1, culturing human foreskin fibroblasts (HFFs): 1, placing children postoperative foreskin in an F12 complete culture medium (95% of DMEM/F12 and 5% of PS); and 2, cutting off and spreading the foreskin in an ultra-clean workbench, washing with PBS with 1% PS twice, cutting off a subcutaneous fat tissue with ophthalmology, cutting into the size of 3 mm*3 mm, and covering with 0.2% of neutral protease at the temperature of 4 DEG C overnight; and S2, reprogramming the HFFs into nerve cells. According to the method, the human fibroblasts can be promoted to be reprogrammed as the mature nerve cells with a collagen type I matrix (Col) at 1 kPa, nearly 100% Tuj1+ nerve cells can be obtained, and the efficiency is high; the mature nerve cells expressing SYN can beobtained in 10 days, and the time is short.