MicroRNA-181a (miR-181a) is upregulated in osteosarcoma, and its overexpression promotes the proliferation and inhibits the apoptosis of osteosarcoma cells. However, the mechanism of miR‑181a as an oncogene remains to be fully elucidated in osteosarcoma. Cleavage factor (CF) Im25 links alternative polyadenylation to glioblastoma tumor suppression, however, its role in osteosarcoma has not been reported. In the present study, it was confirmed that the expression of miR‑181a was upregulated in osteosarcoma, and that silencing miR‑181a inhibited the proliferation and promoted the apoptosis of osteosarcoma cells. miRNAs are short non‑coding RNAs, which regulate target mRNAs by binding predominantly to the 3'untranslated region (3'UTR), inducing either translational repression or degradation of the target. In the present study, target genes of miR‑181a were screened using miRanda, which is a commonly used prediction algorithm. It was found that miR‑181a targeted the 3'UTR of CFIm25 mRNA. Subsequent experiments confirmed that miR‑181a downregulated the expression of CFIm25 in osteosarcoma cells. Finally, it was demonstrated that the CFIm25 protein was also downregulated in osteosarcoma tissues, and inhibited the proliferation and promoted the apoptosis of the cells. Elucidating the roles of miR‑181a and CFIm25 in osteosarcoma not only assists in further understanding the pathogenesis and progression of this disease, but also offers novel targets for effective therapies.