Objective To evaluate the impact of miR-148a on hepatic ischemia/reperfusion (I/R) injury via inhibiting Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα), and analyze the potential mechanism. Methods Liver I/R model was built in mice. Expression of CaMKIIα was detected in the hepatic tissues by Western blotting. The mRNA levels of miR-148a, CaMKIIα, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were analyzed by quantitative real-time PCR (qRT-PCR). HE staining was performed to observe morphological changes of the livers in each group. TUNEL was used to evaluate the degree of hepatocellular apoptosis in each group. Results After hepatic I/R injury, the expression of miR-148a increased, and it was negatively correlated with CaMKIIα. After therapy with exogenous miR-148a mimics, the protein expression of CaMKIIα, the mRNA levels of TNF-α and IL-1β, the degree of inflammatory cell infiltration and liver cell necrosis, and the level of hepatocellular apoptosis were all downregulated. Conclusion The miR-148a may alleviate hepatic I/R injury in mouse by inhibiting CaMKIIα.