In this study, we validated the down-regulation of miR-101 in ESCC tissue specimens and cell lines; investigated the inhibitory effect of miR-101 on ESCC cell proliferation, migration and invasion in vitro; further examined the anti-tumor activity of miR-101 in vivo in a xenograft nude mouse model of ESCC; and verified that miR-101 inhibited ESCC via inhibiting COX-2 expression. The gene discussed is PTGS2; the disease is esophageal squamous cell carcinoma.