Objective To investigate whether EID2B affects tumor cell migration within the colon adenocarcinoma (COAD) immune microenvironment, and to provide a reference for subsequent research in this field. Methods The expression levels of EID2B in COAD were analyzed using the TCGA database, along with its relationship to clinical staging and survival curves; the HPA database was interrogated for analyze the protein expression levels of EID2B; the TIMER database was utilized to analyze the correlation between EID2B and immune cell infiltration; the TCGA database was applied to enrichment analysis of EID2B biological processes; in vitro experiments involved the design of siRNA transfection in THP-1 induced macrophages to knock down EID2B expression, with RT-qPCR detecting the efficiency of EID2B knockdown. Scratch assays and Transwell assays were conducted to evaluate the impact on the migration ability of HCT116 cells. Results EID2B is underexpressed in COAD (P<0.05), correlated with lymph node metastasis (P<0.05), and significantly correlated with macrophage infiltration (P<0.05). The culture supernatant from EID2B knockdown macrophages promoted the migration of HCT116 cells (P<0.05). Conclusion EID2B underexpression is associated with lymph node metastasis in COAD, and knocking down EID2B promotes tumor migration.