Aim: To screen and identify serum microRNAs (miRNAs) that might be used as promising biomarkers for hereditary nonpolyposis colorectal cancer using miRNA array and qRT-PCR. Methods: Four serum samples from patients with hereditary nonpolyposis colorectal cancer and three serum samples from healthy controls were used to identify potential markers by miRNA array. The results of miRNA array were confirmed by qRT-PCR. Results: We found 57 up-regulated miRNAs and 30 down-regulated miRNAs by miRNA array, and 8 miRNAs were chosen for further analysis. Three target gene prediction programs were used to predict target genes of these 8 miRNAs, and 294 genes were predicted, all of which were target genes of mir-20a-5p, mir-548b-5p and mir-548as-3p. qPCR analysis confirmed that serum mir-548as-3p was significantly higher in patients with hereditary nonpolyposis colorectal cancer. Conclusion: Our study demonstrates that serum miRNAs are differentially expressed in patients with hereditary nonpolyposis colorectal cancer, and that mir-548as-3p can potentially serve as a noninvasive biomarker for this disease. © 2013 Baishideng. All rights reserved.