Colorectal cancer (CRC) ranks the third in cancers and the second in the reasons of cancer-related death. More evidence indicates that long non-coding RNA participates in tumor initiation and progression. It's known that cancer susceptibility candidate 9 is an oncogenic long non-coding RNA in CRC. miR-542-3p is a negative regulator of CRC, while integrin-linked kinase could contribute to tumor progression and chemoresistance. However, the correlation among long non-coding RNA cancer susceptibility candidate 9, miR-542-3p and integrin-linked kinase in CRC is still unclear. We demonstrated long non-coding RNA cancer susceptibility candidate 9 in CRC specimens and cell lines overexpressed via real-time quantitative polymerase chain reaction. Once long non-coding RNA cancer susceptibility candidate 9 was knocked down, it significantly inhibited proliferation, invasion, and migration of CRC cells in real-time quantitative polymerase chain reaction, cell counting kit-8, 5-ethynyl-2'-deoxyuridine, and transwell assays, which also was validated in vivo. Long non-coding RNA cancer susceptibility candidate 9 negatively regulates miR-542-3p in a targeted manner, and the function of up-regulated miR-542-3p was confirmed similarly. While miR-542-3p negatively regulates integrin-linked kinase. Thus, we further verified that overexpression of integrin-linked kinase on down-regulated long non-coding RNA cancer susceptibility candidate 9 or up-regulated miR-542-3p significantly restored CRC cell proliferation via bioinformatic analysis, dual-luciferase report assay, real-time quantitative polymerase chain reaction, RNA immunoprecipitation, and western blot. This study testified that silencing long non-coding RNA cancer susceptibility candidate 9 could inhibit proliferation and invasion of CRC cells by miR-542-3p/integrin-linked kinase.