Inflammatory signals originating from colorectal cancer cells have a vital role in the development of colorectal cancer (CRC). microRNAs (miRNAs) have been demonstrated to be involved in the development and progression of CRC. miRNA-142-3p (miR-142-3p) has been reported to be a modulator of inflammatory signals. It has also been shown that miR-142-3p is downregulated in CRC and it acts to be a tumor suppressor. In the present study, interleukin-1 receptor-associated kinase 1 (IRAK1), a key mediator of NF-κB pathway, was identified as a direct target of miR-142-3p. It was also found that miR-142-3p repressed the activation of NF-κB signal induced by LPS in colorectal cancer cells, therefore reducing the expression of inflammatory cytokines, such as IL-6, IL-8, MCP-1, CCL5 and CSF-1. Thus, it is believed that miR-142-3p is a key component in the regulation of NF-κB activity and its anti-inflammatory role may contribute to its suppression of carcinogenesis of CRC.