In summary, our research provides evidence that lncRNA HOXC‐AS1 promotes ESCC development by interacting with RNA‐binding protein IGF2BP2 to stabilize SIRT1 mRNA expression, indicates that HOXC‐AS1‐IGF2BP2‐SIRT1 axis may serve as a potential prognostic marker and therapeutic target for ESCC. Here, PTGDR is linked to esophageal squamous cell carcinoma.