Despite these limitations, our preliminary findings suggest that the two tagging variants of rs3112270 A > G and rs2171513 G > A in the BTLA gene might contribute to the progression of ESCC in the eastern Chinese population, which is the first study for the involvement of the co‐inhibitory BTLA SNPs in ESCC to our knowledge. This evidence concerns the gene BTLA and esophageal squamous cell carcinoma.