Suberoylanilide hydroxamic acid (SAHA) is a histone deacetylase inhibitor (HDACI) with antitumor effects that is being explored as a therapeutic drug. However, it has been reported that non-small cell lung cancer (NSCLC) is resistant to HDACIs. MicroRNAs (miRNAs) are a key class of small, non-coding RNA molecules that modulate post-transcriptional regulation of gene expression in multi-cellular organisms. miRNA expression patterns are involved in deregulation of gene expression in human lung cancer. Here we identified miRNA expression profile changes in response to SAHA treatment in the human lung carcinoma cell line A549. We also examined potential mRNA targets of SAHA-responsive miRNAs by using a target prediction program. Using microarray analysis, we found 64 miRNAs with >2-fold expression changes in SAHA-treated A549 cells. Among them, two unique miRNAs were altered in 2.5 microM SAHA-treated cells, 31 unique miRNAs were altered in 5.0 microM SAHA-treated cells and 31 miRNAs were altered with both doses. These miRNAs are predicted to have several target genes related to angiogenesis, apoptosis, chromatin modification, cell proliferation and differentiation. In conclusion, we have identified a unique set of miRNAs and their expression profiles that are influenced significantly by SAHA in the A549 NSCLC cell line model, which might provide useful information for understanding the anticancer mechanism of SAHA.