To explore the effect of porcine epidemic diarrhea virus(PEDV)on microRNA expression profiles of porcine kidney 15cell(PK-15),total RNA was isolated from PK-15 cells with or without PEDV infection. Then, we obtained the miRNAs by using solexa sequencing technology and analyzed these differentially expressed miRNAs. Heatmap cluster analysis and GO (ontology, GO) (Gene function, MF, Molecular) analysis was performed on the significant differences in expression of the miRNA, and 10 significant differences in expression of miRNA were selected by RT-qPCR. The result showed 214 kinds of microRNAs (miRNAs) expression levels were significantly different in PEDV-infected cells, compared with normal PK-15 cells. Among of them,175 kinds of miRNAs were significantly up-regulated while 39 kinds of miRNAs were significantly down-regulated. Furthermore, qPCR results of the expression trends of miRNA were similar with that of solexa sequencing. Heatmap cluster analysis showed that the vast majority of the viral groups were differentially expressed in miRNA compared with the control group, Go analysis showed that miRNAs are widely involved in combination, binding protein, protein kinase activity, transfer enzyme activity, phosphorus containing radicals transfer, phosphotransferase enzyme activity and other biological effects. The expression trends of RT-qPCR verified by miRNA were consistent with the high throughput sequencing results. The results showed that the swine epidemic diarrhea virus infection had a significant impact on the level of miRNA expression in PK-15 cells, thus providing a new idea for the further study of the miRNA preparation for the treatment of PEDV.