Colorectal cancer (CRC) is the third most common cancer with a very poor prognosis predominantly due to its high rate of tumor invasion and migration, and its resistance to anti‑epidermal growth factor receptor (EGFR) therapy. Although CRC has been widely studied, the underlying molecular mechanism remains to be elucidated. MicroRNA (miR)‑133b has been demonstrated to act as a tumor suppressor in several human cancer types by regulating EGFR. However, the detailed involvement of miR‑133b and EGFR in CRC cells remain to be elucidated. The present study used reverse transcription quantitative polymerase chain reaction and characterized the downregulation of the expression levels of miR‑133b in CRC tissues and cell lines. Cell functional assays demonstrated that restored expression of miR‑133b inhibited the growth and invasion of CRC cells. In addition, a luciferase reporter assay revealed that miR‑133b directly targeted EGFR and repressed its expression levels in CRC cells. Additionally, combination treatment with miR‑133b mimics and the monoclonal anti‑EGFR antibody, cetuximab, which is approved and frequently used for treating patients with CRC, exhibited improved inhibitory effects on the growth and invasion of CRC cells compared with treatment with either alone. Taken together, the present study characterized the role of the miR‑133b/EGFR interaction in CRC cells and this suggested the combinational therapy with cetuximab and miR‑133b was positive and may be a potential novel treatment for patients with CRC in the future.