PURPOSE: Colorectal cancer (CRC) is a frequent malignant tumor with high death rate and poor prognosis. Few reports have explored the association between CRC development and long non-coding (lnc) RNAs expression. This study focused on the important role of a novel lncRNA XIST in the development of CRC. METHODS: To investigate the function of long lncRNA XIST in CRC, its expression level was monitored in both CRC cells and 50 pairs of human CRC tissues and adjacent tissues by RT-qPCR. Moreover, the associations between lncRNA XIST expression level and clinicopathological characteristics and 5-year survival rate of CRC patients were evaluated. Furthermore, function assays containing cell proliferation assay, flow cytometry and colony formation were conducted to investigate the role of lncRNA XIST in CRC. Western blotting assay and luciferase assay were used to explore the regulation mechanism of lncRNA XIST in the development. RESULTS: The expression level of XIST was significantly increased in both CRC tissues sample and CRC cells. XIST promoted CRC cell proliferation by affecting the cell cycle. In addition, XIST and miR-132-3p were inhibited by each other reciprocally. MAPK1 was proved to be a direct target spot of miR-132-3p. We claim that XIST was responsible for CRC cell proliferation working by the miR-132-3p/MAPK1 axis. CONCLUSION: The present study suggests that lncRNA XIST is a potential oncogene in CRC, and could promote CRC cell proliferation through inhibiting miR-132-3p, which may provide a new therapeutic target of CRC.