Long non-coding RNAs (lncRNAs) serve crucial roles in cancer development and progression. lncRNA-activated by transforming growth factor-β (lncRNA-ATB) mediates cell proliferation. However, the association between lncRNA-ATB and human colorectal cancer (CRC) is not completely understood. Therefore, the present study aimed to investigate the role of lncRNA-ATB in CRC, as well as the underlying mechanism. 50 pairs of tumor tissues and adjacent normal tissues from patients with primary CRC were collected. The expression of lncRNA-ATB and microRNA (miR)-141-3p in CRC tissues, adjacent normal tissues and cell lines was detected using reverse transcription-quantitative PCR. CCK-8, colony formation, Transwell, western blot, dual luciferase reporter gene, RNA immunoprecipitation and immunohistochemistry staining assays were conducted to assess the biological function of lncRNA-ATB and miR-141-3p in CRC progression. lncRNA-ATB was upregulated in CRC tissues and cell lines compared with healthy tissues and cells, respectively. Moreover, high expression of lncRNA-ATB was significantly associated with advanced TNM stage and metastasis in CRC. In addition, the results indicated that lncRNA-ATB expression predicted the prognosis and overall survival of patients with CRC. Compared with small interfering RNA-negative control, lncRNA-ATB knockdown inhibited CRC cell proliferation, migration and invasion, whereas, compared with vector, lncRNA-ATB overexpression promoted CRC cell proliferation, migration and invasion. Furthermore, the in vivo experiment suggested that lncRNA-ATB knockdown inhibited tumor growth. The results also indicated that lncRNA-ATB may contribute to CRC progression via binding to tumor suppressor microRNA-141-3p. Collectively, the present study suggested a crucial role of lncRNA-ATB in CRC tumorigenesis, suggesting that lncRNA-ATB may serve as an important marker for the diagnosis and development of CRC.