To determine if long-chain non-coding RNA (lncRNA) MIR4435-2HG (MIR4435) expression is associated with pre-malignant colon polyps and colon cancer. Children's colonic-polyp specimens were sequenced for MIR4435 expression. LncRNA MIR4435 expression data in colorectal cancer and normal intestinal tissues were retrieved from The Cancer Genome Atlas (TCGA). The proliferation, adhesion, and invasion ability of human colon-cancer cell line HCT116 with or without MIR4435 knockdown was analyzed. The expression of Smad4, desmoplakin, and β-catenin genes was detected by western blotting in HCT116 cells. MIR4435 expression correlated with the size of intestinal polyps in children. Expression of MIR4435 was up-regulated in colorectal cancer. MIR4435 knockdown in HCT116 cells inhibited their proliferation, adhesion, and invasion ability. Smad4 and desmoplakin were up-regulated and β-catenin was down-regulated in HCT116 cells by MIR4435 knockdown. MIR4435 expression correlated with the size of intestinal polyps in children and with the proliferation, adhesion, and invasion ability of colon-cancer cells and was upregulated in colon cancer.