Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies worldwide. Long noncoding RNA (lncRNA) MALAT1 acts as an essential oncogene lncRNA (onco-lncRNA) in the development of ESCC. Down-regulation of onco-lncRNA MALAT1 mediated by microRNA-101 (miR-101) and microRNA-217 (miR-217) has been proved to effectively suppress ESCC. In this study, poly(glycidyl methacrylate)-based star-like polycations with flanking folic acid (FA) ligands and rich hydrophilic hydroxyl groups (denoted as s-PGEA-FA) were proposed as efficient nanovectors to deliver miR-101 and miR-217 for silencing onco-lncRNA MALAT1 in different ESCC cells. The inhibition of ESCC by s-PGEA-FA/miRNA nanocomplexes would be achieved via subsequently targeting onco-lncRNA MALAT1 in ESCC cells. To evaluate the ESCC tumor-suppressing efficacy mediated by s-PGEA-FA/miRNA nanocomplexes, a series of assays were carried out, including gene transfection, cell proliferation, cell migration, and cell invasion. The results revealed that s-PGEA-FA-mediated miR-101 and miR-217 delivery effectively inhibited ESCC development, indicating the s-PGEA-FA nanovector was promising for future ESCC therapy.