AIM: To explore the effect of pinobanksin-3-acetate (PB3A) on microRNA (miRNA) expression profile of human colon cancer cells for providing new methods of treatment of colon cancer and development of targeted drug.METHODS: The method of miRNA expression profiling was used to observe the miRNA differential expression in human colon cancer SW480 cells after treated with PB3A.The expression of miRNA-198 and miRNA-296-5p in the SW480 cells was detected by RT-qPCR.The network databases of miRWalk, MicroT, miRanda and so on were used to predict the target genes regulated by these miRNAs, and pathway significant enrichment analysis was performed.RESULTS: miRNA microarray analysis showed that after treated with propolis flavonoid PB3A for 24 h, 267 miRNAs with differential expression twice or more in the SW480 cells were observed.Among them, there were 30 miRNAs with 10-fold or more differential expression, in which 28 were up-regulated and 2 were down-regulated.The results of RT-qPCR showed that the expression levels of miRNA-198 and miRNA-296-5p were consistent with the results of miRNA microarray analysis, and the difference was statistically significant (P<0.05).Bioinformatic analysis revealed that miRNA-198 has 859 target genes, and miRNA-296-5p has 906 target genes.The target genes of miRNA-198 were clustered in pathways in cancer, axon guidance, Wnt signaling pathway, regulation of actin cytoskeleton, insulin signaling pathway and MAPK signaling pathway, while the target genes of miRNA-296-5p were clustered in axon guidance, Wnt signaling pathway, MAPK signaling pathway, endocytosis, melanogenesis, insulin signaling pathway and calcium signaling pathway.CONCLUSION: Propolis flavonoid PB3A affects the expression of miRNA in colon cancer SW480 cells.The abnormal expression of miRNA-198 and miRNA-296-5p may be involved in the inhibitory effect of PB3A on colon cancer.