Our results showed that the expression of GPNMB in ESCC tissues was higher than that in adjacent tissues; the expression rate of GPNMB in primary ESCC patients was 96.5% (218/226); the expression of GPNMB was correlated with the AJCC stage, lymph node metastasis, and degree of differentiation. Here, GPNMB is linked to esophageal squamous cell carcinoma.