Long non-coding RNAs (lncRNAs) are associated with a spectrum of biological processes such as gene regulation on transcriptional and post-transcriptional levels. The HOXA transcript at the distal tip (HOTTIP) lncRNA plays an important role in carcinogenesis; however, the underlying role of HOTTIP in colorectal carcinoma (CRC) remains unknown. The aim of the present study was to evaluate the expression and function of HOTTIP in CRC. In the present study, we analyzed HOTTIP expression levels of CRC patients in tumor and adjacent normal tissue by real-time quantitative PCR. Knockdown of HOTTIP by RNA interference was performed to explore its roles in cell proliferation, migration, and invasion. Our results found that HOTTIP was upregulated in human primary CRC tissues. Knockdown of HOTTIP inhibited CRC cell proliferation, migration, and invasion. Above all, knockdown of HOTTIP could represent a rational therapeutic strategy for CRC.