Here, we demonstrated that 1) PSMA3-AS1 expression is higher in ESCC tissues than in adjacent non-tumor tissues; 2) higher PSMA3-AS1 indicated a poor prognosis in ESCC patients; and 3) PSMA3-AS1 sponges miR-101 to promote the proliferation, invasion, and metastasis of ESCC via up-regulating enhancer of zeste homolog 2 (EZH2) expression. The gene discussed is PSMA3; the disease is neoplasm.