Based on the ESCC cohort size and the detailed mechanism, UCA1, HCP5, and PTCSC1 possess great potential as a therapeutic target for ESCC in association with the Wnt/ β-catenin and PI3K/Akt/mTOR pathways, which signifies the clinical potential of lncRNAs for the treatment of ESCC patients. Here, HCP5 is linked to esophageal squamous cell carcinoma.