〔Abstract〕 Objective To study the mechanism of neurotrophin receptor-interacting MAGE homolog(NRAGE) on the proliferation and invasion of colorectal cancer(CRC) cells. Methods The clinicopathological data of 84 CRC patients were selected. Fluorescence quantitative PCR(qPCR) and Western blot were used to detect the expression of NRAGE in CRC tissues and adjacent normal tissues. The relationship between the expression of NRAGE in cancer tissues and clinicopathological characteristics was analyzed statistically. RT-PCR and Western blot were used to detect the expression of NRAGE mRNA and protein in CRC tumor cell lines HT29, SW480, SW620, LOVO and colorectal normal cell line FHC. MTT proliferation experiment and Transwell migration experiment were used to observe the tumor cell proliferation and migration ability of the NC group, overexpression NRAGE group and NRAGE knockdown group. The expression differences of AKT, p-AKT, ERK1/2, p-ERK1/2, E-cadherin, N-cadherin and Vimentin were detected by qPCR and Western blot. Results Compared with adjacent tissues, NRAGE mRNA and protein expression in CRC cancer tissues were significantly higher. The expression of NRAGE in cancer tissues was related to tumor stage, distant metastasis and lymph node metastasis(allP<0.05). Compared with FHC cells, CRC tumor cell lines HT29, SW480, SW620, and LOVO cells had higher NRAGE mRNA and protein expression(P<0.05). Compared with the NC group, the proliferation and migration ability of CRC tumor cells in the overexpression NRAGE group was significantly enhanced, while the knockdown group was significantly weakened. Compared with the NC group, the SW480 cells in the overexpression NRAGE group had higher p-ERK1/2 protein expression, but there was no significant difference in the expression of ERK1/2, AKT and p-AKT. After the SW480 cells in the overexpression NRAGE group were treated with ERK inhibitor U0126, the proliferation and migration ability of SW480 cells significantly reduced. Conclusion NRAGE can promote the epithelial-mesenchymal transition of CRC cells and enhance the proliferation and migration of CRC tumor cells by activating ERK signaling pathway.