MicroRNAs are a class of small noncoding RNA which play important regulatory roles in a variety of cancers. MiRNA-specific expression profiles have been reported for several pathological conditions. In this study, we combined large scale parallel Solexa sequencing to identify 11 up-regulated miRNAs and 19 down-regulated miRNAs with computational techniques in the sera of ovarian cancer patients while using healthy serum as the control. Among the above, four miRNAs (miR-22, miR-93, miR-106b, miR-451) were validated by quantitative RT-PCR and found to be significantly aberrantly expressed in the serum of ovarian cancer patients (P<0.05). There were no significant differences between samples from cancer stage I/II and III/IV. However, the levels of miR-106b (p=0.003) and miR-451 (p=0.007) were significantly different in those patients under and over 51 yearsof age. MiR-451 and miR-93 were also specific when analyzed with reference to different levels of CA125. This study shows that Solexa sequencing provides a promising method for cancer-related miRNA profiling, and selectively expressed miRNAs could be used as potential serum-based biomarkers for ovarian cancer diagnosis.