〔Abstract〕 Objective To investigate the expression of LAMP5 in colorectal cancer(CRC) and the relationship between the expression of LAMP5 and prognosis of patients with colorectal cancer, reveal the role of LAMP5 in the progression of CRC. Methods GEPIA and LinkedOmics database were used to analyze the expression of LAMP5 in CRC tissues and paired adjacent tissues, and the correlation with clinical parameters and the prognosis of CRC patients followed by validation of clinical samples. Gene Set Enrichment Analysis was used to study the LAMP5 related molecular functions and related signal pathways involved in the occurrence and development in CRC. Results The results of immunohistochemistry showed that the expression of LAMP5 in CRC tissues was significantly higher than that in paired adjacent normal tissues(n=120,P<0.05). LAMP5 expression in CRC tissues was negatively correlated with the degree of differentiation(P<0.05), and positively correlated with N stage and M stage(P<0.05), but not correlated with age, gender and T stage. GEPIA and clinical tissues analysis showed that CRC patients with high expression of LAMP5 had shorter overall survival and disease-free survival than those with low expression of LAMP5(P<0.05). Cox Proportional Hazards Model analysis revealed that the High expression level of LAMP5 was an independent risk factor for OS and DFS in CRC patients(P<0.05).GO analysis showed that LAMP5 had significant correlation with extracellular matrix, extracellular matrix adhesion, extracellular matrix localization, and collagen localization in CRC(P<0.05). KEGG analysis showed that LAMP5 might be involved in multiple pathways, including TGF-β and PI3 K-AKT signaling pathways(P<0.05). Conclusion The expression of LAMP5 is up-regulated in CRC, and correlated with tumor dedifferentiation, lymph node metastasis, distant metastases, and prognosis. Therefore, LAMP5 can be used as a novel biomarker for diagnosis, treatment and prognosis of CRC.