Objective · To analyze the expression of lnc-MTBP-5 in colorectal cancer (CRC), and explore the effect of lnc-MTBP-5 on the invasion of CRC cells and its potential mechanism. Methods · Bioinformatics data from PRJNA218851 and PRJNA376161 data sets were extracted from the Sequence ReadArchive (SRA) database to screen CRC metastasis associated lncRNAs. The Cancer Genome Atlas (TCGA) was used to analyze the expression of lnc-MTBP-5 in CRC tissues and normal tissues, its relationship with the prognosis of patients, and its correlation with metastasis related factors. Quantitative real-time PCR (qPCR) was used to detect the expression of lnc-MTBP-5 in normal intestinal epithelial cells and CRC cells, as well as 53 CRC tissues and para-cancer mucosa. After lnc-MTBP-5 was down-regulated in CRC cells, CCK-8 assay, clone formation and Transwell assay were performed to observe the effect of lnc-MTBP-5 on the proliferation and invasion ability of CRC cells. Results · Lnc-MTBP-5 was associated with CRC metastasis. The expression of lnc-MTBP-5 was significantly increased in 5 CRC cell lines and CRC tissues. Compared with patients with low expression of lnc-MTBP-5, CRC patients with high expression of lnc-MTBP-5 were younger, had higher American Joint Committee on cancer (AJCC) staging, and were prone to metastasis. Lnc-MTBP-5 was positively correlated with CRC metastasis associated in colon cancer 1 (MACC1), mesenchymal to epithelial transition factor (MET) and cadherin-associated protein. After lnc-MTBP-5 was down-regulated, the invasion ability of CRC cells decreased. Conclusion · Lnc-MTBP-5 is up-regulated in CRC cell lines and CRC tissues, and it is negatively correlated with the prognosis of patients. Lnc-MTBP-5 can promote the invasion ability of CRC cells, which may be related to MACC1-HGF (hepatocyte growth factor)/MET pathway.