Activation of innate and acquired immune responses is regulated by detailed mechanisms to control their onset and termination. MicroRNAs have been implicated as negative regulators controlling the diverse of biophysical and biochemical processes at the post-transcriptional level. However, the physiological roles of miRNAs in aquatic organisms are largely unclear. In this study, we explored the potential roles of mmi-miR-192 in regulating interleukin 1 receptor type I (IL-1RI) involved in immune and inflammatory response in miiuy croakers. This was further evaluated by negative expression profiles in both LPS exposure macrophages and Vibrio anguillarum challenged miiuy croaker. By means of promoter analysis, mmi-miR-192 was found to be an AP-1 dependent gene. Importantly, the dual luciferase reporter assay presented the regulation between mmi-miR-192 and IL-1RI. The result of miiuy croaker miR-192 reduced the wild-type IL-1RI but not the mutant one luciferase levels suggested that mmi-miR-192 modulated IL-1RI expression by directly targeting the 3′UTR of IL-1RI mRNA. Overall, our study revealed the mechanism that the miR-192-IL1RI pathway regulated bacteria infection in miiuy croakers.