Background. The mechanism of inflammatory reaction after intracerebral hemorrhage remains unclear, which to some extent restrains the therapeutic development of hemorrhagic stroke. The present study attempts to verify whether NLRP6 plays an important role in inflammatory reaction after intracerebral hemorrhage and identify the critical microRNA during the process.Methods. Suitable simulated cerebral hemorrhage environments were establishedin vitroandin vivo. BV2 cells were treated with hemin to induce cell damage. Collagenase was used to establish a model of mouse cerebral hemorrhage. The relationship among NLRP6, miR-331-3p, and the corresponding inflammatory expression was closely observed during this process. Techniques, such as western blot, real-time quantitative PCR, immunofluorescence, and immunocytochemistry, were used to detect the expression of relative genes and molecules in thein vitroandin vivomodels.Results. Downregulated miR-331-3p increased the expression of NLRP6 and alleviated the expression of TNF-alpha and IL-6. The neurological function recovery of mice was promoted after intracerebral hemorrhage.Conclusion. miR-331-3p regulated the inflammatory response after cerebral hemorrhage by negatively regulating the expression of NLRP6.