This investigation was intended to elucidate whether long noncoding RNA (lncRNA)‐activated by transforming growth factor‐β (ATB) interacting with miR‐200c could mediate colorectal cancer (CRC) progression, offering potential strategies for diagnosing and treating CRC. Here totally 315 patients with CRC were recruited, and their CRC tissues and adjacent normal tissues were gathered. Concurrently, four colon cancer cell lines (ie, SW620, Lovo, HCT116, and SW480) and the human colon mucosal epithelial cell line (NCM460) were also purchased. Moreover, si‐ATB, si‐NC, miR‐200c mimic, miR‐200c inhibitor, and miR‐NC were prepared for transfection into the CRC cells, and their effects on CRC cell lines were evaluated based on the conduction of 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, colony formation assay, and flow cytometry assay. Eventually, the Luciferase reporter gene assay was carried out to judge if there existed a targeted relationship between ATB and miR‐200c. The results of Cox regression analyses suggested that overexpressed lncRNA ATB, underexpressed miR‐200c, poor tumor differentiation, lymph‐vascular invasion, and perineural invasion were symbolic of shortened survival of the patients with CRC (all P < .05). Besides, transfection of pcDNA3.1‐ATB and miR‐200c inhibitor could boost the viability and proliferation of Lovo and SW620 cell lines (all P < .05). Meanwhile, the expressions of p53 and p21 were also reduced under treatments of pcDNA3.1‐ATB and miR‐200c inhibitor (P < .05). In addition, CDK2 seemed to reverse the contribution of miR‐200c to intensifying viability and proliferation of Lovo and SW420 cell lines (P < .05). Furthermore, ATB might downregulate miR‐200c expression by targeting it (P < .05), and CDK2 was subjected to dual regulation of both ATB and miR‐200c (P < .05). In conclusion, the lncRNA ATB/miR‐200c/CDK2 signaling was responsible for intensified proliferation and prohibited apoptosis of CRC cells, which might provide effective approaches for diagnosing and treating CRC.