Mechanistically, we demonstrated that the interplay between c-Met receptor tyrosine kinase and HOTAIR is critical for maintenance of hybrid E/M state in HCC cells to cope with rate-limiting steps of tumor metastasis, such as survival in adhesion independent microenvironment, escaping from anoikis and resisting to fluidic shear stress (FSS) in HCC. Here, HOTAIR is linked to neoplasm.