Esophageal cancer (EC) is among the deadliest malignancies in humans, with various miRNAs shown to regulate its progression by targeting distinct genes. miR-508-5p was identified as being linked to the malignant behavior of various tumors. Nevertheless, the precise role and mechanism of miR-508-5p in esophageal cancer (EC) remain ambiguous. This investigation focuses on the role and mechanism of the miR-508-5p/TSGA10 axis in the progression of EC. The expression of miR-508-5p and TSGA10 in EC cell lines was evaluated using quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Cell transfection techniques were used to knock down miR-508-5p and observe its effects on cell proliferation, migration, invasion, and apoptosis. A dual-luciferase reporter gene assay was conducted to verify the targeting relationship of miR-508-5p with TSGA10. Co-culture studies were undertaken to examine the regulatory effect of the miR-508-5p/TSGA10 axis on the polarization state of tumor-associated macrophages (TAMs) and the malignant behavior of EC cells. The expression of miR-508-5p was significantly elevated in EC cells. Knocking down miR-508-5p curbed cell proliferation, migration, and invasion while promoting apoptosis. TSGA10 was validated as a primary target gene of miR-508-5p. miR-508-5p knockdown could inhibit the M2 polarization of TAMs by upregulating TSGA10, thereby suppressing the tumorigenic behavior of EC cells. miR-508-5p promotes the M2 polarization of TAMs and enhances the malignant behavior of EC cells by inhibiting TSGA10.