Colorectal cancer (CRC) is a leading cause of cancer-related deaths. Long non-coding RNAs are emerging as key regulators in cancer by modulating functions of microRNAs thereby affecting expression of genes involved in the pathogenesis of cancers. Since the CTHRC1 gene (Collagen Triple‑Helix‑Repeat Containing‑1) encodes an extracellular matrix protein involved in collagen regulation and cell migration, this study investigated the role of LINC01748 in CRC and its interaction with the Let-7b-5p/CTHRC1 axis. RNA sequencing data from The Cancer Genome Atlas database was analyzed to identify differentially expressed lncRNAs, miRNAs, and mRNAs in CRC. Interactions between LINC01748, miRNAs, and mRNAs were predicted, a protein-protein interaction network was constructed, and functional enrichment analysis was performed to reveal the biological activity of target genes. Additionally, the expression of LINC01748, Let-7b-5p, and CTHRC1 in CRC tissues and adjacent non-cancerous tissues were determined using RT-qPCR and western blotting. Collagen density was also evaluated by histopathological examination. 107 differentially expressed lncRNAs, 313 miRNAs, and 1,479 mRNAs were identified in CRC samples. Bioinformatics analysis indicated that LINC01748 may function as a competing endogenous‑RNA for Let-7b-5p, regulating CTHRC1 expression. RT-qPCR confirmed upregulation of LINC01748 and CTHRC1 and downregulation of Let-7b-5p in CRC. Significant positive correlation of LINC01748 with CTHRC1, and a negative correlation with Let-7b-5p were detected. Gene Ontology and KEGG pathway analysis suggested the involvement of LINC01748/Let-7b-5p/CTHRC1 axis in ECM organization and collagen content. This study revealed the role of LINC01748 in the Let-7b-5p/CTHRC1 axis, highlighting its clinical significance in CRC.