Objective: To investigate the role of DISP3 in thyroid cancer (TC) progression and its modulation of the tumor immune microenvironment. Methods: Bioinformatics analyzed DISP3 expression and its prognostic significance in TC. The biological impact of DISP3 on TC cells was validated through in vitro assays and in vivo BALB/c mice models. Flow cytometry and cytokine assays were performed to evaluate the regulatory mechanism of DISP3 on dendritic cell (DC) maturation and macrophage polarization. Results: DISP3 was overexpressed in TC and significantly correlated with poorer prognosis. Bioinformatics revealed that DISP3 expression negatively correlated with DC and macrophage infiltration. Experimentally, knocking down DISP3 significantly inhibited TC cell proliferation and migration both in vitro and in vivo. Furthermore, DISP3 knockdown enhanced anti-tumor cytokine secretion, promoted DC maturation, and induced a phenotypic shift of macrophages toward the M1 (anti-tumor) phenotype. Conclusion: DISP3 promotes TC progression by modulating the immune microenvironment, specifically by suppressing DC maturation and M1 macrophage polarization. These findings suggest DISP3 as a promising novel target for TC immunotherapy.