MicroRNA (miR)‑744‑5p serves a pivotal role in the progression of multiple cancers; however, the function of miR‑744‑5p in colorectal cancer (CRC) remains largely unknown. In the present study, the effects of miR‑744‑5p on the progression of CRC were analyzed and the mechanisms involved were investigated. It was revealed that miR‑744‑5p was frequently downregulated in CRC tissues and cell lines. Overexpression of miR‑744‑5p significantly inhibited the proliferation, colony formation, and promoted the apoptosis of CRC cells. Bioinformatics analysis revealed that Septin 2 (SEPT2) was a potential target of miR‑744‑5p. miR‑744‑5p bound the 3'‑untranslated region (UTR) of SEPT2 and reduced the level of SEPT2 in CRC cells. A negative correlation between the expression of miR‑744‑5p and SEPT2 was observed in CRC tissues. Overexpression of SEPT2 counteracted the suppressive effect of miR‑744‑5p on the proliferation and apoptosis of CRC cells. Collectively, these data demonstrated the functional mechanism of miR‑744‑5p by targeting SEPT2, which suggested miR‑744‑5p as a potential target for the treatment of patients with CRC.