For the first time, a ceRNA model of the HOTAIR/miR-125 and miR-143/HK2 regulatory axis was elucidated, in which HOTAIR acts as a competing endogenous RNA by sponging miR-125/miR-143 to promote HK2 expression, thereby facilitating the tumourigenesis of ESCC in vitro and in vivo. The gene discussed is HOTAIR; the disease is esophageal squamous cell carcinoma.