According to our findings, overexpression of linc00261 induced an epithelial-like appearance, inhibited the tumor spheres formation, and also abolished TGF-β1-induced EMT, migration, and invasion in SMMC-7721; moreover, both linc00261 knockdown and overexpression affect the mRNA and protein expressions of the EMT-TFs (Slug and ZEB1) and CSCs-TFs (OCT4 and SOX2), the core downstream targets of TGF-β1 pathway, besides, the activated TGF-β1 signaling after linc00261 knockdown was blocked by TGF-βR inhibitor, SB431542. This evidence concerns the gene LINC00261 and neoplasm.