Objective To investigate the effect of miRNA-384 ( miR-384) expression on hepatic steatosis in mice with nonalcoholic fatty liver disease ( NAFLD) induced by high-fat diet ( HFD) . Methods A total of 30 male C57 BL/6 J mice were fed for 7 days to adapt to the environment and then randomly divided into 2 groups, with 15 mice in each group. The mice in the control group were given normal diet, and those in the model group were given HFD for 8 weeks and then the liver tissue was harvested. HE and Nile red staining were used to observe the pathological changes of the liver. Microarray sequencing was performed to determine the whole-genome miRNA expression profile of liver tissue, and PCR was used to measure the relative expression of miR-384. The t-test was used for the comparison of continuous data between groups. Results In the control group, the liver was red with sharp edges, the lobular structure was clear, and there was no hepatic steatosis; in the model group, the liver was yellow with blunt edges, and the hepatocytes were swollen with a large number of fat vacuoles in the cytoplasm and nuclear deviation caused by the fusion of lipid droplets. Compared with the normal mice, the NAFLD mice had 12 upregulated miRNAs and 18 downregulated miRNAs in liver tissue. Some of the differentially expressed miRNAs between the control group and the model group were screened to obtain the same cluster diagram. Among the 8 miRNAs with significant changes, miR-384 showed a significant fold change. Conclusion The upregulation of miR-384 is closely associated with hepatic steatosis, but its mechanism still needs further study.