Matrix metalloproteinases (MMPs) are involved in the cleavage of several components of the extracellular matrix and serve important roles in tumor growth, metastasis and invasion. Previous studies have focused on the expression of one or several MMPs in esophageal squamous cell carcinoma (ESCC); however, in the present study, the transcriptomics of all 23 MMPs were systematically investigated with a focus on the prognostic value of the combination of MMPs. In this study, 8 overlapping differentially expressed genes of the MMP family were identified based on data obtained from Gene Expression Omnibus and The Cancer Genome Atlas. The prognostic value of these MMPs were investigated; the receiver operating characteristic curves, survival curves and nomograms showed that the combination of 6 selected MMPs possessed a good predictive ability, which was more accurate than the prediction model based on Tumor-Node-Metastasis stage. Gene set enrichment analysis and gene co-expression analysis were performed to investigate the potential mechanism of action of MMPs in ESCC. The MMP family was associated with several signaling pathways, such as epithelial-mesenchymal transition (EMT), Notch, TGF-beta, mTOR and P53. Cell Counting Kit-8, colony formation, wound healing assays and western blotting were used to determine the effect of BB-94, a pan-MMP inhibitor, on proliferation and migration of ESCC cells. BB-94 treatment decreased ESCC cell growth, migration and EMT. Therefore, MMPs may serve both as diagnostic and prognostic biomarkers of ESCC, and MMP inhibition may be a promising preventive and therapeutic strategy for patients with ESCC.