Colorectal cancer (CRC) ranks as one of the most malignant solid tumors worldwide. Bromodomain containing 8 (BRD8) functions as an oncogene in various cancers. This study aimed to investigate the roles of BRD8 in CRC. mRNA expression was detected using reverse transcription-quantitative PCR (RT-qPCR). Protein expression was detected using Western blot. The expression of macrophage markers was detected using immunohistochemistry and immunofluorescence. Cell viability was detected using Cell Counting Kit-8 (CCK-8) assay. Macrophage function was detected using flow cytometry. Cell migration and invasion was detected using transwell assays. We found that high levels of BRD8 mediated the predominance of M2-like tumor-associated macrophages (TAM2) and predicted poor prognosis of CRC patients. However, BRD8 knockdown suppressed TAM2 polarization as well as the migration and invasion of CRC cells. Mechanically, BRD8-mediated the upregulation of transforming growth factor β1 (TGF-β1), overexpression of which promoted TAM2 polarization and aggressiveness of CRC cells. Taken together, BRD8 deficiency suppressed TAM2 polarization, inhibiting the progression of CRC. Therefore, BRD8 may be a therapeutic target for CRC.