Irritable bowel syndrome (IBS) is a common disorder of unknown etiology. Studies have found a close relation between IBS and microRNAs (miRNAs), but the study concerning the relationship between IBS and miR‐181c‐5p in IBS is still blank. Thus, this study aims to explore the role of miR‐181c‐5p in IBS via interleukin 1α (IL1A). Initially, microarray analysis was used to retrieve the genes related to IBS and to predict miRNAs regulating IL1A gene. IBS model was then established with abdominal withdraw reflection (AWR) and Bristol stool grading in mice measured. Afterwards, the functional role of miR‐181c‐5p in IBS was determined using the ectopic expression, depletion and reporter assay experiments, as well as miR‐181c‐5p and IL1A expression detected. Subsequently, expression of tumor necrosis factor‐α (TNF‐α), interleukin‐2 (IL‐2), and IL‐6 were detected to further determine the effects of miR‐181c‐5p and IL1A on inflammation in IBS. miR‐181c‐5p and IL1A might be involved in IBS. miR‐181c‐5p was found to be decreased while IL1A was increased in IBS rats. In addition, miR‐181c‐5p could target and inhibit expression of IL1A, and IBS mice exhibited elevated AWR and Bristol stool grading, namely 6 to 7 points (70.4 [38 of 54]). Moreover, with the overexpression of miR‐181c‐5p or silencing of IL1A, the expression of TNF‐α, IL‐2, and IL‐6 was decreased. Collectively, this study suggested that overexpressed miR‐181c‐5p could silence IL1A, thus inhibiting low‐grade inflammation in IBS rats. miR‐181c‐5p/IL1A is expected to serve as a novel target for the treatment of IBS.