The present study aimed to investigate the role of microRNA (miR) -141 in the pathogenesis of colorectal cancer (CRC). In total, 58 CRC patients were included in the present study. The mRNA and protein expression levels of mitogen-activated protein kinase 4 (MAP4K4) were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. The miRNA-141 expression was measured by RT-qPCR, while serum MAP4K4 content was detected by enzyme-linked immunosorbent assay. Natural killer (NK) cells and T cells in peripheral blood were detected by flow cytometry. The results indicated that the mRNA and protein expression levels of MAP4K4 were significantly elevated in the tumor tissues, lymph nodes (P< 0.01) and serum (P< 0.05) in CRC. Furthermore, the expression levels of MAP4K4 in CRC patients with lymph node metastasis were higher compared with those in patients without metastasis. Bioinformatics analysis revealed that MAP4K4 may be the target gene of miRNA-141. The expression levels of miRNA-141 in the tumor tissues, lymph nodes and serum were significantly decreased in CRC patients, with a more evident decline in cases with lymph node metastasis. In addition, the percentage of NK, CD3(+) T and CD4(+) T cells was significantly decreased, whilst the number of CD8(+) T cells was significantly increased, in the peripheral blood in CRC. The present results showed that miRNA-141 was downregulated in CRC, which increased the expression levels of MAP4K4 and altered the anti-tumor response, further increasing the proliferation, invasion and metastasis of the tumors. These findings may contribute to improving the current understanding of the pathogenesis of CRC, and lead to the development of therapies involving miRNA-141.